Activation of the YAP/KLF5 transcriptional cascade in renal tubular cells aggravates kidney injury.

The Hippo/YAP pathway plays a critical role in tissue homeostasis. Our previous work demonstrated that renal tubular YAP activation induced by double knockout (dKO) of the upstream Hippo kinases Mst1 and Mst2 promotes tubular injury and renal inflammation under basal conditions. However, the importance of tubular YAP activation remains to be established in injured kidneys in which many other injurious pathways are simultaneously activated. Here, we show that tubular YAP was already activated 6 h after unilateral ureteral obstruction (UUO). Tubular YAP deficiency greatly attenuated tubular cell overproliferation, tubular injury, and renal inflammation induced by UUO or cisplatin. YAP promoted the transcription of the transcription factor KLF5. Consistent with this, the elevated expression of KLF5 and its target genes in Mst1/2 dKO or UUO kidneys was blocked by ablation of Yap in tubular cells. Inhibition of KLF5 prevented tubular cell overproliferation, tubular injury, and renal inflammation in Mst1/2 dKO kidneys. Therefore, our results demonstrate that tubular YAP is a key player in kidney injury. YAP and KLF5 form a transcriptional cascade, where tubular YAP activation induced by kidney injury promotes KLF5 transcription. Activation of this cascade induces tubular cell overproliferation, tubular injury, and renal inflammation.

Role of protease-activated receptor 4 in mouse models of acute and chronic kidney injury.

Protease-activated receptor 4 (PAR4) is a G protein-coupled receptor activated by thrombin. In the platelet, response to thrombin PAR4 contributes to the predominant procoagulant microparticle formation, increased fibrin deposition, and initiation of platelet-stimulated inflammation. In addition, PAR4 is expressed in other cell types, including endothelial cells. Under inflammatory conditions, PAR4 is overexpressed via epigenetic demethylation of the PAR4 gene, F2RL3. PAR4 knockout (KO) studies have determined a role for PAR4 in ischemia-reperfusion injury in the brain, and PAR4 KO mice display normal cardiac function but present less myocyte death and cardiac dysfunction in response to acute myocardial infarction. Although PAR4 has been reported to be expressed within the kidney, the contribution of PAR4 to acute kidney injury (AKI) and chronic kidney disease (CKD) is not well understood. Here we report that PAR4 KO mice are protected against kidney injury in two mouse models. First, PAR4 KO mice are protected against induction of markers of both fibrosis and inflammation in two different models of kidney injury: 1) 7 days following unilateral ureter obstruction (UUO) and 2) an AKI-CKD model of ischemia-reperfusion followed by 8 days of contralateral nephrectomy. We further show that PAR4 expression in the kidney is low in the control mouse kidney but induced over time following UUO. PAR4 KO mice are protected against blood urea nitrogen (BUN) and glomerular filtration rate (GFR) kidney function pathologies in the AKI-CKD model. Following the AKI-CKD model, PAR4 is expressed in the collecting duct colocalizing with Dolichos biflorus agglutinin (DBA), but not in the proximal tubule with Lotus tetragonolobus lectin (LTL). Collectively, the results reported in this study implicate PAR4 as contributing to the pathology in mouse models of acute and chronic kidney injury.NEW & NOTEWORTHY The contribution of the thrombin receptor protease-activated receptor 4 (PAR4) to acute kidney injury (AKI) and chronic kidney disease (CKD) is not well understood. Here we report that PAR4 expression is upregulated after kidney injury and PAR4 knockout (KO) mice are protected against fibrosis following kidney injury in two mouse models. First, PAR4 KO mice are protected against unilateral ureter obstruction. Second, PAR4 KO mice are protected against an AKI-CKD model of ischemia-reperfusion followed by contralateral nephrectomy.

SNHG16/miR-205/HDAC5 is involved in the progression of renal fibrosis.

Renal interstitial fibrosis (RIF) represents an irreversible and progressive pathological manifestation of chronic renal disease, which ultimately leads to end-stage renal disease. Long noncoding RNAs (lncRNAs) have been suggested to be involved in the progression of RIF. Small nucleolar RNA host gene 16 (SNHG16), a member of lncRNAs, has been found to be involved in the progression of pulmonary fibrosis. This paper first researched the effect of SNHG16 on renal fibrosis. We established a unilateral ureteral obstruction (UUO)-induced mouse RIF model by ligation of the left ureter to evaluate the biological function of SNHG16 in RIF. As a result, SNHG16 was upregulated in UUO-induced renal fibrotic tissues. Knockdown of SNHG16 inhibited RIF and reduced alpha-smooth muscle actin (α-SMA), fibronectin, and college IV expression. miR-205 was a target of SNHG16, and downregulated in UUO-induced renal fibrotic tissues. Inhibition of miR-205 promoted RIF and increased the expression of α-SMA, college IV, and fibronectin. Overexpression of SNHG16 promoted the UUO-induced RIF, but miR-205 abrogated this effect of SNHG16. Histone deacetylase 5 (HDAC5) showed high expression in UUO-induced renal fibrotic tissues. Knockdown of HDAC5 significantly reduced α-SMA, fibronectin, and college IV expression in renal tissues of UUO-induced mice. Inhibition of miR-205 promoted HDAC5 expression, but knockdown of SNHG16 inhibited HDAC5 expression in renal tissues of UUO-induced mice. In conclusion, SHNG16 is highly expressed in renal fibrotic tissues of UUO-induced mice. Knockdown of SHNG16 may prevent UUO-induced RIF by indirectly upregulating HDAC5 via targeting miR-205. SHNG16 may be novel target for treating renal fibrosis.

Examining the relationship between parents' self-reported mindfulness and observed language use in attachment-relevant communication.

Parents' language use is an important context for early socialization. We examined the relationship between parents' self-reported mindfulness and observed language use in two forms of attachment-relevant communication. Sixty-three parents of 6-18-month-old infants from Australia (n = 32) and New Zealand (n = 31) completed the five facets of mindfulness-short form (FFMQ-SF) questionnaire, the adult attachment interview (AAI), and a 10-min play session with their infant. We examined parents' frequency of word usage within the categories of the linguistic inquiry word count (LIWC) text analysis program to explore the relationship between mindfulness and language use. Mindfulness was associated with cognitive, affective, perceptual, and time orientation language use in the AAI. However, fewer associations were identified between mindfulness and language use in the parent-infant play session. Results are discussed in terms of their relevance to mindfulness and attachment.

El uso del lenguaje por parte de los padres es un contexto importante para la temprana socialización. Examinamos la relación entre la auto reportada atención consciente de los padres y el observado uso del lenguaje en dos formas de comunicación relevantes a la unión afectiva. Sesenta y tres progenitores de infantes entre 6 y 18 meses de edad de Australia (n = 32) y Nueva Zelanda (n = 31) completaron el cuestionario de Cinco Facetas de la Atención Consciente en su formato corto (FFMQ­SF), la Entrevista de la Afectividad Adulta (AAI), así como una sesión de juego de diez minutos con sus infantes. Examinamos la frecuencia del uso de palabras por parte de los padres dentro de las categorías del programa de análisis de texto Investigación Lingüística del Conteo de Palabras (LIWC) para explorar la relación entre la atención consciente y el uso del lenguaje. Se asoció la atención consciente con el uso del lenguaje cognitivo, afectivo, perceptivo y con orientación del tiempo de la AAI. Sin embargo, menos asociaciones se identificaron entre la atención consciente y el uso del lenguaje en la sesión de juego entre progenitor e infante. Los resultados se discuten en términos de su relevancia para la atención consciente y la afectividad.

Is lower fetal heart rate variability a susceptibility marker to the impact of negative coparenting on infant regulatory capacity?

Lower fetal heart rate variability (FHRV) may be a prenatal endophenotypic susceptibility marker and increase the impact of both positive and negative coparenting on infant regulatory capacity. This study analyzed the moderator role of FHRV in the association between positive and negative coparenting and infant regulatory capacity at 3 months. The sample comprised 86 first-born infants and their mothers and fathers recruited at a public Health Service in Northern Portugal. FHRV was recorded during routine cardiotocography examination at the third trimester of gestation. Mothers and fathers reported on coparenting and infant regulatory capacity at 2 weeks and 3 months postpartum. FHRV moderated the association between mother's and father's negative coparenting at 2 weeks postpartum and infant regulatory capacity at three months. Infants with low FHRV presented higher regulatory capacity when mothers or fathers reported less negative coparenting, while lower regulatory capacity when mothers or fathers reported more negative coparenting, than infants with high FHRV. Findings suggested lower FHRV as a prenatal endophenotypic susceptibility marker that increases the impact of negative coparenting on infant regulatory capacity.

La más baja variabilidad del pulso cardíaco fetal (FHRV) pudiera ser un marcador determinante de la susceptibilidad endofenotípica prenatal y aumentar el impacto de la crianza compartida tanto positiva como negativa sobre la capacidad regulatoria del infante. Este estudio analizó el papel moderador de FHRV en la asociación entre la positiva y negativa crianza compartida y la capacidad regulatoria del infante a los tres meses. El grupo muestra estaba compuesto de 86 infantes primerizos y sus mamás y papás. Se grabó la FHRV durante una examinación de cardiotocografía de rutina en el tercer trimestre de la gestación. Las mamás y los papás reportaron acerca de la crianza compartida y la capacidad regulatoria del infante a las dos semanas y a los tres meses después del parto. La FHRV moderó la asociación entre la crianza compartida negativa de la mamá y del papá a las dos semanas después del parto y la capacidad regulatoria del infante a los tres meses. Los infantes con baja FHRV presentaron una capacidad regulatoria más alta cuando las mamás o los papás reportaron una crianza compartida menos negativa, mientras que la capacidad regulatoria más baja se dio cuando las mamás o los papás reportaron una crianza compartida más negativa, que los infantes con una FHRV alta. Los resultados señalan la más baja FHRV como un marcador determinante de la susceptibilidad endofenotípica prenatal que aumenta el impacto de la crianza compartida negativa sobre la capacidad regulatoria del infante. Los infantes con baja FHRV pueden ser aquellos que mejor desarrollan mecanismos de autorregulación en la presencia de una crianza compartida menos negativa, mientras que están bajo alto riesgo de problemas regulatorios en la presencia de una crianza compartida más negativa.

Une variabilité de la fréquence cardiaque fœtale (VFCF) plus basse pourrait être un marqueur de sensibilité endophénotypique prénatale et augmenter l'impact du coparentage positif et négatif sur la capacité régulatoire du nourrisson. Cette étude a analysé le rôle modérateur de la VFCF dans le lien entre le coparentage positif et négatif et la capacité régulatoire du nourrisson à trois mois. Cet échantillon a inlu 86 nourrisson premiers nés et leurs mères et pères. La VFCF a été enregistrée penfdant un examen de cardiotocographie de routine au troisième trimestre de la grossesse. Les mères et les pères ont fait état de leur coparentage et de la capacité régulatoire du nourrisson à deux semaines et à trois mois postpartum. La VFCF a modéré le lien entre le coparentage négatif de la mère et du père à deux mois postpartum et la capacité régulatoire du nourrisson à trois mois. Les nourrissons avec une VFCF basse ont présenté une capacité régulatoire plus élevée lorsque les mères ou les pères ont signalé moins de coparentage négatif, alors qu'ils ont présenté une capacité régulatoire plus basse lorsque les mères ou les pères ont signalé un coparentage plus négatif, que les nourrissons avec une VFCF élevée. Les résultats ont suggéré une VFCF plus basse comme un marqueur de sensibilité endophénotypique prénatale qui augmente l'impact de coparentage négatif sur la capacité régulatoire du nourrisson. Les enfants avec une VFCF basse peuvent être ceux qui développent mieux leurs mécanismes auto-régulatoires en présence de moins de coparentage négatif, tout en étant à haut risque de problèmes régulatoires en présence de plus de coparentage négatif.

Noninvasive assessment of renal dynamics and pH in a unilateral ureter obstruction model using DCE MR-CEST urography.

PURPOSE: To assess the potential of DCE MR CEST urography for assessing renal function in mice with unilateral ureter obstruction (UUO) by simultaneous pH and renal uptake/clearance measurements following injection of iopamidol. METHODS: The right ureter of nine mice was obstructed via suture ligation. The animals were imaged at day 1, 2, and 3 post-obstruction on an 11.7T MRI scanner. Ninety-six sets of saturated CEST images at 4.3 and 5.5 ppm were collected. Renal pH values were obtained by calculating the signal ratio for these two frequencies and using a pH calibration curve. Renal time activity curves were measured as a percentage change in the post-injection CEST signal at 4.3 ppm relative to the average pre-injection signal. RESULTS: For the healthy mice, the time activity curves of both kidneys were nearly identical and displayed rapid excretion of contrast. For the UUO mice, the dynamic CEST curves for the obstructed kidneys displayed prolonged time to peak (TTP) values and delayed contrast excretion compared with the contralateral (CL) kidneys. Renal pH maps of the healthy animals showed similar acidic values for both kidneys (pH 6.65 ± 0.04 vs 6.67 ± 0.02), whereas in the obstructed kidneys there was a significant increase in pH values compared with the CL kidneys (pH 6.67 ± 0.08 vs 6.79 ± 0.11 in CL and UUO kidneys, respectively). CONCLUSION: Our findings indicate that DCE-MR-CEST urography can detect changes in renal uptake/excretion and pH homeostasis and distinguish between obstructed and unobstructed kidney as early as 1 day after UUO.

Cxcl10 deficiency attenuates renal interstitial fibrosis through regulating epithelial-to-mesenchymal transition.

IFN-γ-inducible protein 10 (IP-10, CXCL10) has been widely demonstrated to be involved in multiple kidney pathological processes. However, the role of CXCL10 in renal fibrosis remains unclear. In this study, Cxcl10-deficient (Cxcl10-/-) mice were used to generate the unilateral ureteral obstruction (UUO) model. The level of renal fibrosis and inflammatory cell infiltration was examined in vivo and the effects of CXCL10 on EMT process of HK-2 cells was investigated in vitro. We observed that the injury degree of renal tissue and the collagen deposition levels were lighter and the expression of α-SMA, collagen I and fibronectin was significantly reduced in Cxcl10-/- mice, while the expression of E-cadherin was increased. However, interstitial F4/80-positive macrophages and CD4-positive T lymphocytes were unaffected by knockout of Cxcl10. Furthermore, IFN-γ or CXCL10 stimulation could obviously promote the expression of α-SMA, collagen I, fibronectin and reduce the expression of E-cadherin in HK-2 cells, which could be inhibited by transfection of Cxcl10-siRNA. Our findings suggested Cxcl10 knockout could reduce renal dysfunction and inhibit renal fibrosis through regulating EMT process of renal tubular epithelial cells in murine UUO model. These results may provide a novel insight into the mechanism and a potential therapy target of renal fibrosis.

Poricoic acid A suppresses renal fibroblast activation and interstitial fibrosis in UUO rats via upregulating Sirt3 and promoting ß-catenin K49 deacetylation.

Renal interstitial fibrosis is the common pathological process of various chronic kidney diseases to end-stage renal disease. Inhibition of fibroblast activation attenuates renal interstitial fibrosis. Our previous studies show that poricoic acid A (PAA) isolated from Poria cocos is a potent anti-fibrotic agent. In the present study we investigated the effects of PAA on renal fibroblast activation and interstitial fibrosis and the underlying mechanisms. Renal interstitial fibrosis was induced in rats or mice by unilateral ureteral obstruction (UUO). UUO rats were administered PAA (10 mg·kg-1·d-1, i.g.) for 1 or 2 weeks. An in vitro model of renal fibrosis was established in normal renal kidney fibroblasts (NRK-49F cells) treated with TGF-ß1. We showed that PAA treatment rescued Sirt3 expression, and significantly attenuated renal fibroblast activation and interstitial fibrosis in both the in vivo and in vitro models. In TGF-ß1-treated NRK-49F cells, we demonstrated that Sirt3 deacetylated ß-catenin (a key transcription factor of fibroblast activation) and then accelerated its ubiquitin-dependent degradation, thus suppressing the protein expression and promoter activity of pro-fibrotic downstream target genes (twist, snail1, MMP-7 and PAI-1) to alleviate fibroblast activation; the lysine-49 (K49) of ß-catenin was responsible for Sirt3-mediated ß-catenin deacetylation. In molecular docking analysis, we found the potential interaction of Sirt3 and PAA. In both in vivo and in vitro models, pharmacological activation of Sirt3 by PAA significantly suppressed renal fibroblast activation via facilitating ß-catenin K49 deacetylation. In UUO mice and NRK-49F cells, Sirt3 overexpression enhanced the anti-fibrotic effect of PAA, whereas Sirt3 knockdown weakened the effect. Taken together, PAA attenuates renal fibroblast activation and interstitial fibrosis by upregulating Sirt3 and inducing ß-catenin K49 deacetylation, highlighting Sirt3 functions as a promising therapeutic target of renal fibroblast activation and interstitial fibrosis.

What works for whom? Mother's psychological distress as a moderator of the effectiveness of a home visiting intervention.

Attachment-based home visiting programs that serve new mothers experiencing psychological distress may advance health equity by helping families systemically exposed to adversity. This study examined whether one such program (Promoting First Relationships/PFR) had particularly beneficial effects on maternal and child relationship outcomes for mothers reporting the greatest psychological distress. A randomized controlled trial of the PFR program included a low-income sample of 252 Spanish- and English-speaking mother-child dyads referred prenatally for mental health concerns. The sample of mothers was 65.5% White, 17.5% Black, and 17.1% multiracial or other racial groups; 47.2% reported Hispanic ethnicity. The moderating variable of psychological distress was measured using maternal-reported screening tools for symptoms of depression, anxiety, anger, post-traumatic stress, and interpersonal sensitivity. Outcomes included observed parenting sensitivity and self-reported understanding of infants/toddlers, caregiving confidence, and child externalizing behavior. Results showed a significant treatment condition by baseline psychological distress interaction for observed parenting sensitivity such that differences in outcomes favoring the PFR condition were greatest among those with high baseline psychological distress (baseline child age 6-12 weeks). In a low-income sample of new mothers, those with the greatest need, as indicated by high psychological distress, showed greater improvements in their sensitive and responsive caregiving if they were randomized to the PFR treatment condition.

Los programas de visita a casa basados en la afectividad que sirven a madres nuevas que experimentan angustia sicológica pudieran mejorar la equidad de salud ayudando a familias sistemáticamente expuestas a circunstancias adversas. Este estudio examinó si uno de tales programas (Promover Primeras Relaciones /PFR) tiene particularmente efectos beneficiosos en los resultados de la relación materna y del niño para madres que reportan la mayor angustia sicológica. Un ensayo controlado al azar sobre el programa PFR incluyó un grupo muestra de bajos recursos económicos de 252 díadas de madre-niño que hablaban español o inglés, referidas prenatalmente por razón de salud mental. El grupo muestra de madres estaba compuesto de 65.5% blancas, 17.5% negras, y 17.1% multirracial o de otros grupos raciales; el 47.2% reportó origen étnico hispano. La variable moderadora de angustia sicológica se midió con herramientas de detección reportadas por las madres para síntomas de depresión, ansiedad, ira, estrés postraumático y sensibilidad interpersonal. Entre los resultados se incluyen la observada sensibilidad de crianza y la auto-reportada comprensión de infantes y niños pequeñitos, la confianza en la prestación de cuidado, así como la conducta de externalización del niño. Los resultados muestran una significativa condición de tratamiento por medio de interacción de angustia sicológica al nivel básico para la observada sensibilidad de crianza, de manera que las diferencias en resultados que favorecen la condición PFR fueron mayores entre quienes presentaban una alta angustia sicológica de base (punto base edad del niño 6 a 12 semanas). En un grupo muestra de madres nuevas de bajos recursos económicos, aquellas con las mayores necesidades, tal como indica la alta angustia sicológica, mostraron mayores logros en su sensibilidad y el cuidado sensible si se les había seleccionado al azar para la condición de tratamiento PFR.

Les programmes de visite à domicile basés sur l'attachement qui servant des nouvelles mères faisant l'expérience de détresse psychologique peuvent faire avancer l'équité en santé en aidant des familles systématiquement exposées à l'adversité. Cette étude a examiné si un tel programme (la Promotion de Premières Relations, soit en anglais Promoting First Relationships/PFR) avait des effets particulièrement bénéfiques sur les résultats de relation maternelle et enfant pour les mères faisant état de la plus grande détresse psychologique. Un essai contrôlé randomisé du programme PFR a inclus un échantillon de 252 dyades mères-enfants de milieu défavorisé, parlant espagnol et anglais, référées avant la naissance pour des problèmes de santé mentale. L'échantillon de mères était 65,5% caucasiennes/blanches, 17,5% noires, and 17,1% multiraciales ou autres groupes raciaux, 47,2% faisant état d'une ethnicité hispanique. La variable modératrice de détresse psychologique a été mesurée en utilisant des outils de dépistage rapportés par la mère de dépression, d'anxiété, de stress post-traumatique, et de sensibilité interpersonnelle. Les résultats ont inclus une sensibilité de parentage observée et une compréhension auto-rapportée des bébés/petits enfants, une confiance de parentage, et un comportement externalisant de l'enfant. Les résultats montrent une condition de traitement importante par l'interaction psychologique de base pour la sensibilité de parentage observée telles que les différences dans les résultats favorisant la condition PFR étaient les plus grandes parmi celles avec la base de détresse psychologique élevée (âge de base de l'enfant 6-12 semaines). Chez un échantillon de nouvelles mères de milieux défavorisés, celles ayant le besoin le plus élevé, indiqué par une haute détresse psychologique, ont fait preuve des plus améliorations dans leur parentage sensible et réactif si elles étaient randomisées pour la condition de traitement PFR.

Looking back to light the path forward: Ghosts in the Nursery revisited.

The infant health movement was launched nearly 50 years ago with the publication of the now classic paper, Ghosts in the Nursery: A psychoanalytic approach to the problems of impaired infant-mother relationships, written by Selma Fraiberg, Edna Adelson, and Vivian Shapiro (1975). This paper offers us lessons for infant mental health practice that have been proven true time and again over the last 50 years. These lessons both underscore the factors essential to clinical progress across a range of interventions, and remind us of the significant challenges we face in these times of massive, global trauma and oppression, extreme economic hardship, and systemic racism. This commentary reviews the key lessons of Fraiberg and her colleagues' classic paper, addresses some of the challenges inherent in retaining the breadth and substance of Fraiberg's model in contemporary practice, and proposes a model for conceptualizing infant and early childhood mental health practice that is geared toward building the relational foundations of reflection (Slade, 2023).

Hace casi cincuenta años que el movimiento de salud infantil se inició con la publicación del ahora clásico ensayo Fantasmas en la guardería: Un acercamiento sicoanalítico a los problemas de relaciones infante-madre deterioradas, escrito por Selma Fraiberg, Edna Adelson y Vivian Shapiro (1975). Fantasmas en la guardería nos ofrece lecciones para la práctica de la salud mental infantil cuya validez ha sido demostrada una y otra vez a lo largo de los últimos 50 años. Estas lecciones enfatizan los factores que son esenciales para el progreso clínico a lo largo de una gama de intervenciones. Ellos también nos recuerdan los retos significativos que enfrentamos en estos tiempos de trauma y opresión global masivas, adversidades económicas extremas y racismo sistémico. Este comentario revisa las lecciones claves del clásico ensayo de Freiberg y sus colegas, se ocupa de algunos de los desafíos inherentes para mantener la amplitud y sustancia del modelo de Freiberg en la práctica contemporánea y propone un modelo para la conceptualización de la práctica de salud mental infantil y la temprana niñez, el cual está dirigido a establecer los cimientos de la reflexión con base en la relación (Slade, 2023) en la práctica clínica.

Le mouvement de la santé du nourrisson a été lancé il y a cinquante ans avec la publication d'un article désormais classique intitulé Fantômes dans la chambre d'enfants: Une approche psychanalytique des problèmes des relations enfants-mères déficientes, écrit par Selma Fraibert, Edna Adelson et Vivian Shapiro (1975). Fantômes dans la chambre d'enfants nous offre des leçons pour la pratique de santé mentale du nourrisson qui se sont avérées vraies au fil des 50 dernières années. Ces leçons soulignent les facteurs essentiels au progrès clinique au travers d'une gamme d'interventions. Elles nous rappellent également les défis importants auxquels nous faisons face à cette époque de trauma et d'oppression massive globale, de difficultés économiques extrêmes et de racisme systémique. Ce commentaire passe en revue les leçons clés de l'article classique de Fraibert et ses collègues, en adressant certains des défis inhérents à la nécessité de retenir l'ampleur et la substance du modèle de Fraiberg dans la pratique contemporaine et en proposant un modèle pour la conceptualisation de la pratique de santé mentale du nourrisson et de la petite enfance qui soit axé sur la construction de fondations relationnelles sur la réflexion (Slade 2023) dans la pratique Clinique.

"You do need to do the interaction": Mothers' perceptions of responsive parenting following a home-based parenting intervention.

Responsive parenting (also known as responsivity) is a dynamic and bidirectional exchange between the parent-child dyad and associated with a child's social and cognitive development. Optimal interactions require a sensitivity and understanding of a child's cues, responsiveness to the child's need, and a modification of the parent's behavior to meet this need. This qualitative study explored the impact of a home visiting program on mothers' perceptions of their responsivity to their children. This study is part of a larger body of research known as right@home, an Australian nurse home visiting program promoting children's learning and development. Preventative programs such as right@home prioritize population groups experiencing socioeconomic and psychosocial adversity. They provide opportunities to promote children's development through the enhancement of parenting skills and an increase in responsive parenting. Semi-structured interviews were conducted with 12 mothers, providing insight into their perceptions of responsive parenting. Four themes were extracted from the data using inductive thematic analysis. These indicated that: (1) mothers' perceived preparation for parenting, (2) recognition of mother and child needs, (3) response to mother and child needs, and (4) motivation to parent with responsiveness, were considered important. This research highlights the importance of interventions that focus on the parent-child relationship in increasing mother's parenting capabilities and promoting responsive parenting.

La crianza con sensibilidad (también conocida como crianza con capacidad de respuesta) es un dinámico intercambio en ambas direcciones entre la díada progenitor-niño, asociada con el desarrollo social y cognitivo del niño. Las interacciones óptimas requieren de una sensibilidad y comprensión de las señales del niño, capacidad de respuesta a la necesidad del niño, y de una modificación del comportamiento del progenitor para cumplir con esta necesidad. Este estudio cualitativo exploró el impacto de un programa de visita a casa sobre las percepciones de las madres acerca de su capacidad de respuesta a sus niños. Este estudio es parte de un mayor cuerpo investigativo conocido como right@home (justo en casa), un programa australiano de visita a casa por parte de enfermeras que promueve el aprendizaje y desarrollo de los niños. Los programas preventivos tales como right@home dan prioridad a grupos de población que experimentan adversidad socioeconómica y sicosocial. Ellos ofrecen oportunidades para promover el desarrollo de los niños por medio del mejoramiento de las habilidades de crianza y un incremento de la sensibilidad en la crianza. Se llevaron a cabo entrevistas semiestructuradas con 12 madres, lo cual aportó ideas sobre sus percepciones de la crianza con sensibilidad. Se extrajeron cuatro temas de la información usando análisis temáticos inductivos. Estos indicaron que se consideraban importantes (1) el cómo las madres percibían su preparación para la crianza, (2) el reconocimiento de las necesidades de la madre y del niño, (3) la respuesta a las necesidades de la madre y del niño, y (4) la motivación a criar con sensibilidad. Esta investigación subraya la importancia de intervenciones que se enfoquen en la relación progenitor-niño para aumentar las capacidades de crianza de la madre y promover una crianza con sensibilidad.

Le parentage réactif (aussi connu comme réactivité) est un échange dynamique et bidirectionnel entre la dyade parent-enfant, et lié au développement social et cognitive d'un enfant. Les interactions optimales demandent une sensibilité et une compréhension des signaux de l'enfant, la réactivité au besoin de l'enfant, et une modification du comportement du parent pour répondre à ce besoin. Cette étude qualitative a exploré l'impact d'un programme de visite à domicile sur les perceptions des mères de leur réactivité à leurs enfants. Cette étude fait partie de recherches plus étendues connues sous le nom de de right@home, un programme de visite infirmières à domicile australien promouvant l'apprentissage et le développement des enfants. Les programmes de prévention tels que right@home privilégient les groupes de population marqués par l'adversité socioéconomique et psychosociale. Ils offrent des opportunités de promouvoir le développement des enfants au travers du renforcement des capacités de parentage et une augmentation du parentage réactif. Des entretiens semi-structurés ont été faits avec 12 mères, offrant un aperçu de leurs perceptions du parentage réactif. Quatre thèmes ont été extraits des données en utilisant une analyse thématique inductive. Ces dernières ont indiqué que (1) la préparation perçue des mères pour le parentage, (2) la reconnaissance des besoins de la mère et de l'enfant, (3) la réponse aux besoins de la mère et de l'enfant, et (4) la motivation du parent avec la réaction ont toutes été considérées comme importantes. Ces recherches mettent en lumière l'importance d'interventions qui se concentrent sur la relation parent-enfant en augmentant les capacités de parentage des mères et en promouvant le parentage réactif.

Enhancing early parenting in the community: Preliminary results from a learning collaborative approach to scale up Attachment and Biobehavioral Catch-up.

Attachment and Biobehavioral Catch-up (ABC) is a promising home-visiting intervention promoting sensitive caregiving and secure parent-child attachment in families with young children. The goal of this study was to examine a learning collaborative approach to disseminating ABC in a community setting. Training outcomes (e.g., trainee completion, satisfaction, effectiveness of training methods) and intervention outcomes (e.g., parent behavior, parent beliefs, child socioemotional development) were examined. Eighteen practitioners participated in the ABC learning collaborative; 13 completed training. Quantitative and qualitative measures indicated that trainees were satisfied with their experience and valued the unique collaboration opportunities offered by the learning collaborative. In addition, trainees served 67 families in the community, 37 of whom completed all sessions of ABC. The study was conducted in the United States. Racial demographics of the children in the sample included: 56.7% White, 22.4% Black/African-American, 17.9% Bi- or Multi-racial, and 3.0% unknown. Regarding ethnicity, 80.6% were Non-Hispanic/Latino, 10.4% were Hispanic/Latino, and 9.0% were unknown. Caregivers who completed ABC showed more sensitive parenting behavior and reported positive changes in their perceived self-efficacy and their beliefs around infant crying. Children who received ABC showed increased socioemotional functioning. Results demonstrate successful dissemination of ABC in the community using a learning collaborative approach.

El Alcance de Afectividad y Bio-comportamiento (ABC) es una prometedora intervención de visita a casa que promueve el cuidado sensible y una relación progenitor-niño segura en familias con niños pequeños. El propósito de este estudio fue examinar un acercamiento de aprendizaje colaborativo para diseminar el ABC en un escenario comunitario. Se examinaron los resultados de entrenamiento (v.g. que el entrenado completó el proceso, satisfacción, efectividad de los métodos de entrenamiento) y los resultados de intervención (v.g. comportamiento del progenitor, creencias del progenitor, desarrollo socioemocional del niño). Dieciocho profesionales en la práctica participaron en el proceso de aprendizaje colaborativo; 13 completaron el entrenamiento, Las medidas cuantitativas y cualitativas indicaron que quienes se entrenaban estaban satisfechos con su experiencia y valoraron las oportunidades de colaboración que el proceso de aprendizaje colaborativo ofrecía de manera única. Adicionalmente, quienes se entrenaban les sirvieron a 67 familias en la comunidad, 37 de las cuales completaron todas las sesiones del ABC. El estudio se llevó a cabo en los Estados Unidos. Los perfiles demográficos raciales de los niños incluyen: 56.7% de raza blanca, 22.4% de raza negra o Afroamericanos, 17.9% birraciales o multirraciales, con un 3.0% cuya raza se desconoce. En cuanto a la etnicidad, 80.6% no eran hispanos o latinos, 10.4% eran hispanos o latinos, con un 9.0% cuya etnicidad se desconoce. Los cuidadores que completaron el ABC mostraron una conducta de crianza más sensible y reportaron cambios positivos en cuanto a su percepción de auto efectividad y su creencia acerca del llanto del infante. Los niños que recibieron el ABC mostraron un aumento en su funcionamiento socioemocional. Los resultados demuestran una exitosa diseminación del ABC en la comunidad usando un acercamiento de aprendizaje colaborativo.

L'attachement et le rattrapage bio-comportemental (en anglais Attachment and Biobehavioral Catch-up, soit ABC) est une intervention prometteuse de visite à domicile promouvant des soins sensibles et un attachement parent-enfant sécure chez les familles avec de jeunes enfants. Le but de cette étude est d'examiner une approche collaborative d'apprentissage à la dissémination de l'ABC dans le contexte d'une communauté. Les résultats de la formation (par exemple le fait de terminer le stage, la satisfaction, l'efficacité des méthodes de formation) et les résultats de l'intervention (par exemple le comportement du parent, les croyances parentales, le développement socio-émotionnel de l'enfant) ont été examinés. Dix-huit praticiens ont participé à la collaboration d'apprentissage ABC; 13 ont terminé la formation. Les mesures quantitatives and qualitatives ont indiqué que les stagiaires étaient satisfaits de leur expérience et avaient apprécié la chance d'une collaboration unique offerte par la collaboration d'apprentissage. De plus les stagiaires ont aidé 67 familles dans la communauté, 37 d'entre elles ayant terminé toutes les séances de l'ABC. L'étude a été faite aux Etats-Unis d'Amérique. Les données démographiques raciales des enfants dans l'échantillon ont inclus: 56,7% blancs, 22,4% noirs américains, 17,9% métisses ou multi-ethniques, et 3,0% de race inconnue. Concernant l'ethnicité, 80,6% était Non-Hispaniques/Non-Latinos, 10,4% étaient Hispaniques/Latinos et 9,0% étaient d'une ethnicité inconnue. Les personnes prenant soin des enfants qui ont complété l'ABC ont fait preuve d'un comportement de parentage plus sensible et fait état de changements positifs dans leur auto-efficacité perçue et leurs croyances concernant les pleurs des bébés. Les enfants ayant reçu l'ABC ont démontré un fonctionnement socio-émotionnel plus élevé. Les résultats démontrent une dissémination réussie de l'ABC dans une communauté en utilisant une approche collaborative d'apprentissage.

DC: 0-5 system in clinical assessment with specialty pediatric populations.

Early childhood mental health (ECMH) programs provide an opportunity to provide specialized mental health services to vulnerable young children and connect them with necessary evidence-based early intervention. However, there is a paucity of descriptive and explorative studies of the clinic protocols in the literature. Even within published work, there is a lack of standardization in clinical models and diagnostic systems limiting comparison and extrapolation. This paper describes how the DC: 0-5 framework guides the development of the model for an ECMH clinic embedded in the context of academic pediatrics. It also highlights the opportunity the DC 0-5 presents for developing the standardized protocols and a mechanism for standardized data collection in clinical settings. The paper demonstrates the utility of using the DC 0-5 in protocol development, assessment and data collection the mental health assessments of 87 children ages 0-6 were reviewed to gather information on history, presenting problems, parent-child relationship, and mental health diagnoses. This paper and associated data underscore the utility and necessity of ECMH clinics while identifying challenges in the field.

Los programas de salud mental en la temprana niñez ofrecen una oportunidad para proveer servicios de salud mental especializados a niños pequeños vulnerables y ponerlos en contacto con la necesaria intervención temprana que se base en la evidencia. Sin embargo, hay escasez de estudios descriptivos y de exploración de los protocolos clínicos en la información impresa. Aun dentro de los trabajos publicados, se da una falta de estandarización en los modelos clínicos y sistemas de diagnóstico, lo cual limita la comparación y la extrapolación. Este ensayo describe cómo el marco de trabajo DC: 0-5 guía el desarrollo del modelo para una clínica de salud mental en la temprana niñez enmarcado dentro del contexto de la pediatría académica. También resalta la oportunidad que DC 0 a 5 presenta para desarrollar los protocolos estandarizados y un mecanismo para la recolección de datos estandarizados en escenarios clínicos. El ensayo demuestra la utilidad de usar el DC 0 a 5 en el desarrollo de protocolos, evaluación y recolección de datos. Se revisaron las evaluaciones de salud mental de 87 niños de edad 0-6 para obtener información acerca del historial, la presentación de problemas, la relación progenitor-niño y la diagnosis de salud mental. Este ensayo y la información asociada subraya la utilidad y necesidad de las clínicas de salud mental en la temprana niñez, al tiempo que identifica los retos en el campo.

Les programmes de santé mentale de la petite enfance offrent une chance d'offrir des services spécialisés de santé mentale à des jeunes enfants vulnérables et de les connecter à une intervention précoce ayant des preuves à l'appui. Cependant, dans les recherches, il existe très peu d'études descriptives et exploratoires des protocoles cliniques. Même au sein du travail qui est publié, nous observons un manque de standardisation dans les modèles cliniques et dans les systèmes diagnostiques, limitant la comparaison et l'extrapolation. Cet article décrit comment la structure DC: 0-5 guide le développement du modèle pour une clinique de santé mentale de la petite enfance ancrée dans le contexte de la pédiatrie académique. L'article met également en lumière l'opportunité que présente la DC 0 à 5 pour le développement de protocoles standardisés et un mécanisme pour une collecte de données standardisée dans des contextes cliniques. Nous démontrons l'utilité de l'utilisation de la DC 0 à 5 dans le développement du protocole, l'évaluation et la collecte de données. Les évaluations de santé mentale de 87 enfants âgés de 0-6 ont été passées en revue afin de récolter des données sur l'histoire, ce qui présente des problèmes, la relation parent-enfant, et les diagnostics de santé mentale. Cet article et les données qui y sont liées soulignent l'utilité et la nécessité des cliniques de santé mentale de la petite enfance tout en identifiant les défis qui se présentent dans ce domaine.

Self-report measure of parental reflective functioning: A study of reliability and validity across three samples of varying clinical risk.

The Parental Reflective Functioning Questionnaire (PRFQ) provides an efficient way to measure a parent's capacity to recognize their child's mental states and to understand the relationship between underlying mental states and behavior. To date, limited work evaluates its psychometric properties beyond initial validation studies. Here we examined the reliability and validity of the PRFQ in three samples of varying clinical risk (e.g., community sample, previous mental health diagnosis, substance use disorder diagnosis). Across samples, the majority (e.g., 75%-78%) of mothers identified as White; all mothers were from the USA. We compared the PRFQ to task-based measures of mentalization, the Parent Development Interview (PDI), and measures of the parent-child relationship. The PRFQ was a reliable measure across samples, and it was associated in theoretically consistent ways with task-based measures of mentalization. Parental RF across the PDI and PRFQ were not highly correlated in a sample of mothers with substance use disorders. Existing RF measures may be tapping into a different component of the broader construct of parental reflective functioning (PRF). The PRFQ was further validated by demonstrating relationships with parent-report measures of the parent-child relationship. Taken together, these findings provide additional support for the reliability and validity of the PRFQ.

El Cuestionario del Funcionamiento con Reflexión del Progenitor (PRFQ) aporta una manera eficaz de medir la capacidad del progenitor para reconocer los estados mentales de su niño y comprender la relación entre los estados mentales subyacentes y el comportamiento. A la fecha, un trabajo limitado evalúa sus propiedades sicométricas más allá de los estudios de validación inicial. Aquí examinamos la confiabilidad y validez del PRFQ en tres grupos muestra de riesgo clínico variado (v.g. grupo comunitario, previa diagnosis de salud mental, diagnosis de trastorno por uso de sustancias). A través de los grupos muestra, la mayoría (v.g., 75-78%) de las madres se identifican como blancas; todas las madres eran de los Estados Unidos. Comparamos el PRFQ con medidas de mentalización basadas en tareas, la Entrevista del Desarrollo del Progenitor (PDI), y medidas de la relación progenitor-niño. El PRFQ fue una medida confiable a lo largo de los grupos muestra, y se asoció de maneras teoréticamente consistentes con las medidas de mentalización basadas en tareas. El funcionamiento con reflexión del progenitor a lo largo del PDI y PRFQ no se correlacionaron altamente en un grupo muestra de madres con trastornos de uso de sustancias. Las medidas del funcionamiento con reflexión existentes pudieran sacar provecho de un componente diferente de la más amplia edificación del funcionamiento con reflexión del progenitor. Se validó además el PRFQ por medio de demostrar las relaciones con las medidas auto reportadas por el progenitor de la relación progenitor-niño. Tomados en conjunto, estos resultados aportan un apoyo adicional para la confiabilidad y validez del PRFQ.

Le Questionnaire de Fonctionnement de Réflexion Parental (QFRP) offre une manière efficace de mesurer la capacité d'un parent à reconnaître les états mentaux de leur enfant et de comprendre la relation entre les états mentaux sous-jacents et le comportement. Jusqu'à présent peu d'études ont évalué ses propriétés psychométriques au-delà des études initiales de validation. Nous examinons ici la fiabilité et la validité du QFRP chez trois échantillons de risque clinique varié (soit un échantillon communautaire, un diagnostic de santé mentale précédent, un diagnostic de trouble lié à l'usage d'une substance). Au travers des échantillons la majorité (c'est-à-dire 75-78%) des mères se sont identifiées comme étant blanches et toutes les mères étaient américaines (des USA). Nous avons comparé le QFRP à des mesures de mentalisation faites à partir d'une tâche, à l'Entretien de Développement du Parent (en anglais Parent Development Interview, soit PDI), et à des mesures de la relation parent-enfant. Le QFRP s'est avéré être une mesure fiable au travers des échantillons et était lié de manières théoriquement cohérentes à des mesures de mentalisation (basées sur des tâches). Le FR parental au travers du PDI et le QFRP n'étaient pas fortement liés chez un échantillon de mères avec un trouble lié à l'usage d'une substance. Il est possible que les mesures FR qui existent puisent dans un composant différent de la structure plus large du fonctionnement de réflexion parental, Le QFRP a été en outre validé par la démonstration de la relation entre les mesures rapportées par les parents de la relation parent-enfant. Pris dans l'ensemble ces résultats offrent un soutien supplémentaire pour la fiabilité et la validité du QFRP.

The role of murine M1 macrophages from different sources in unilateral ureteral obstruction.

Introduction: The unilateral ureteral obstruction (UUO) model is the most extensively used model to investigate chronic renal fibrosis. Macrophages play a critical role in the UUO model. We aimed to analyze the phenotype of macrophages from different sources activated in vitro and explore the role of M1 macrophages from various sources in UUO. Material and methods: C57BL/6 mice were randomly allocated to five different groups (n = 5 per group): the sham-operated control group, PBS-treated (UUO + PBS) group, bone marrow-derived M1 macrophage-treated (UUO + BM1) group, peritoneal M1 macrophage-treated (UUO + PM1) group, and splenic M1 macrophage-treated (UUO + SPM1) group. After M1 macrophages were injected into the tail vein of UUO-treated mice, renal fibrosis indexes were determined using HE, Masson staining, and α-SMA. Results: Compared to those in the UUO + PBS group, the pathological changes were much more severe in the UUO + BM1, UUO + PM1, and UUO + SPM1 groups. Compared to that in the UUO + PBS group, UUO + BM1 group, and UUO + SPM1 group, the collagen area in the UUO + PM1 group was higher at post-UUO day 5 (p < 0.01). The expression of α-SMA in the UUO + PM1 group was higher than that in the UUO + PBS group, UUO + BM1 group, and UUO + SPM1group (p < 0.001). Conclusions: The M1 macrophages cultured in vitro were reinjected into mice and aggravated kidney injury and fibrosis. Compared with BM1 and SPM1, PM1 demonstrated a stronger effect on inducing renal injury and fibrosis.

Hydroxychloroquine alleviates renal interstitial fibrosis by inhibiting the PI3K/Akt signaling pathway.

Renal fibrosis is the ultimate presentation of chronic kidney disease, which progresses to end-stage renal disease. Hydroxychloroquine (HCQ) has been adapted for the treatment of autoimmune diseases; however, the potential mechanism underlying the role of HCQ in renal fibrosis remains unclear. C57BL/6 J mice were randomly divided into three groups (sham group, UUO group, and UUO + HCQ group (20 mg/kg)). HE and Masson staining were performed to assess kidney tissue damage and fibrosis, and western blotting was performed to assess the expression of epithelial-mesenchymal transition (EMT), extracellular matrix (ECM), PI3K/AKT, and NF-κB-related proteins. PCR and TUNEL were adopted to detect inflammatory factors and cell apoptosis. HK-2 cells treated with TGF-ß1 were used for the in vitro experiments. HCQ may potentially have therapeutic effects on renal fibrosis mediated through 122 target genes, and the Kyoto Encyclopedia of Genes and Genomes pathways of these genes were enriched for PI3K/AKT signaling based on network pharmacology. UUO mice that received HCQ demonstrated significantly less tubular damage than the UUO mice. HCQ treatment additionally blunted EMT in UUO kidneys and TGF-ß1-treated renal tubular epithelial cells, and alleviated ECM deposition in kidney tissue. Furthermore, HCQ treatment reduced UUO-induced inflammation and apoptosis. Mechanistically, HCQ treatment suppressed the activation of the PI3K/Akt and NF-kB pathways. This study demonstrated that HCQ ameliorated renal fibrosis by inhibiting the PI3K/AKT and NF-κB signaling pathways to attenuate inflammatory factors and the apoptotic function of renal tubular epithelial cells, thus providing renewed theoretical evidence for HCQ treatment of renal fibrosis.

IL-33 attenuates renal fibrosis via group2 innate lymphoid cells.

Renal fibrosis is a common pathway in the progression of various kidney diseases and injuries. Unilateral ureteral obstruction (UUO) induces renal fibrosis, and immune responses profoundly affect its pathogenesis. Group2 innate lymphoid cells (ILC2s) are strongly activated by interleukin (IL) -33, which is a member of IL-1 family and recognize as alarmin. ILC2s quickly produce large amounts of type 2 cytokines including IL-5 and IL-13, which are involved in inflammation, tissue homeostasis, and wound healing. However, the relationship between renal fibrosis and ILC2s has been unclear. In the present study, we investigated the roles of the ILC2/L-33 axis in renal fibrosis using a UUO model. We found that kidney ILC2s decreased in UUO-affected kidneys compared with their counterpart kidneys despite IL-33 upregulation. There was no effect of reactive oxygen species or TGF-ß from reduced ILC2 caused by UUO. Pretreatment with IL-33 before UUO induced ILC2s and Tregs in kidneys and alleviated renal fibrosis. Furthermore, this protective effect was maintained even when CD4+T cells was depleted. These findings demonstrated that ILC2s play a predominant role in the suppressive function of renal fibrosis mediated by pretreatment with IL-33. In contrast, post-treatment with IL-33 after UUO increased ILC2s in kidneys but had no therapeutic effect on renal fibrosis. Our findings suggest that ILC2s have potential roles in the prevention of renal fibrosis and can serve as a therapeutic and diagnostic target.

Pharmacological targeting macrophage phenotype via gut-kidney axis ameliorates renal fibrosis in mice.

Renal fibrosis is a non-negligible pathological change in chronic kidney disease (CKD). Increasing evidence indicates that macrophage and gut-kidney axis are correlated with CKD. In this study, we manifest that pharmacological modulating macrophage phenotype via gut-kidney axis is conducive to the alleviation of renal fibrosis. Employing wild-type male mice with unilateral ureteral obstruction (UUO), renal fibrosis was dramatically mitigated in mice treated with antibiotics. And antibiotics application restricted the synthesis of intestinal flora metabolite Trimethylamine N-Oxide (TMAO). However, a 1.3% choline diet enhanced fibrosis. Then we further examined macrophage phenotype through the gut-kidney axis. In in vivo and in vitro culture experiments, the mRNA expression of Nos2, Tnf-α, Il-6, and Il-1ß increased under TMAO stimulation. Curbing the NLRP3 inflammasome countered TMAO-induced M1 polarization in bone marrow-derived macrophages. This finding demonstrates that NLRP3 plays a critical part in macrophage polarization. Because of the declining M1 polarization trend in the early stage, M2 macrophages undoubtedly decreased in the tissues. Our results revealed that some metabolites could regulate macrophage phenotype, which matters the severity of renal fibrosis. Thus, pharmacological targeting macrophage phenotype via gut-kidney axis may be a different strategy to treat renal fibrosis.

Synthetic Non-Coding RNA for Suppressing mTOR Translation to Prevent Renal Fibrosis Related to Autophagy in UUO Mouse Model.

The global burden of chronic kidney disease is increasing, and the majority of these diseases are progressive. Special site-targeted drugs are emerging as alternatives to traditional drugs. Oligonucleotides (ODNs) have been proposed as effective therapeutic tools in specific molecular target therapies for several diseases. We designed ring-type non-coding RNAs (ncRNAs), also called mTOR ODNs to suppress mammalian target rapamycin (mTOR) translation. mTOR signaling is associated with excessive cell proliferation and fibrogenesis. In this study, we examined the effects of mTOR suppression on chronic renal injury. To explore the regulation of fibrosis and inflammation in unilateral ureteral obstruction (UUO)-induced injury, we injected synthesized ODNs via the tail vein of mice. The expression of inflammatory-related markers (interleukin-1ß, tumor necrosis factor-α), and that of fibrosis (α-smooth muscle actin, fibronectin), was decreased by synthetic ODNs. Additionally, ODN administration inhibited the expression of autophagy-related markers, microtubule-associated protein light chain 3, Beclin1, and autophagy-related gene 5-12. We confirmed that ring-type ODNs inhibited fibrosis, inflammation, and autophagy in a UUO mouse model. These results suggest that mTOR may be involved in the regulation of autophagy and fibrosis and that regulating mTOR signaling may be a therapeutic strategy against chronic renal injury.