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1.
Development ; 151(17)2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39254648

RESUMO

During embryonic development, Wnt signaling influences both proliferation and sensory formation in the cochlea. How this dual nature of Wnt signaling is coordinated is unknown. In this study, we define a novel role for a Wnt-regulated gene, Mybl2, which was already known to be important for proliferation, in determining the size and patterning of the sensory epithelium in the murine cochlea. Using a quantitative spatial analysis approach and analyzing Mybl2 loss-of-function, we show that Mybl2 promoted proliferation in the inner sulcus domain but limited the size of the sensory domain by influencing their adjoining boundary position via Jag1 regulation during development. Mybl2 loss-of-function simultaneously decreased proliferation in the inner sulcus and increased the size of the sensory domain, resulting in a wider sensory epithelium with ectopic inner hair cell formation during late embryonic stages. These data suggest that progenitor cells in the inner sulcus determine boundary formation and pattern the sensory epithelium via MYBL2.


Assuntos
Proliferação de Células , Cóclea , Proteína Jagged-1 , Células-Tronco , Animais , Cóclea/embriologia , Cóclea/citologia , Cóclea/metabolismo , Camundongos , Epitélio/embriologia , Epitélio/metabolismo , Células-Tronco/citologia , Células-Tronco/metabolismo , Proteína Jagged-1/metabolismo , Proteína Jagged-1/genética , Regulação da Expressão Gênica no Desenvolvimento , Via de Sinalização Wnt , Padronização Corporal/genética , Transativadores/metabolismo , Transativadores/genética , Células Ciliadas Auditivas Internas/metabolismo , Células Ciliadas Auditivas Internas/citologia , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética
2.
Parasite ; 31: 53, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39240136

RESUMO

BACKGROUND: Clonorchis sinensis is a zoonotic liver fluke that inhabits the bile ducts of the human liver for prolonged periods, leading to cholangiocarcinoma. Recent research indicates associations between altered biliary microbiota and bile duct disorders. However, the impacts of C. sinensis infection on bile duct epithelium and subsequent effects on biliary microbiota remain unknown. METHODS: Feline bile duct samples were collected from both uninfected and C. sinensis-infected cats. Histopathological examination was performed to assess epithelial changes, fibrosis, mucin and cell proliferation using hematoxylin-eosin staining and immunohistochemistry. Additionally, biliary microbiota composition was analyzed through 16S rRNA gene sequencing. Statistical analyses were conducted to compare the microbial diversity and relative abundance between infected and uninfected samples. RESULTS: Histopathological analysis of infected feline bile ducts revealed prominent epithelial hyperplasia characterized by increased cell proliferation. Moreover, periductal fibrosis and collagen fibrosis were observed in infected samples compared to uninfected controls. Biliary microbial richness decreased with disease progression compared to uninfected controls. Streptococcus abundance positively correlated with disease severity, dominating communities in cancer samples. Predictive functional analysis suggested that C. sinensis may promote bile duct lesions by increasing microbial genes for carbohydrate metabolism, replication, and repair. CONCLUSIONS: This study provides comprehensive insights into the pathological effects of C. sinensis infection on feline bile duct epithelium and its influence on biliary microbiota composition. These novel findings provide insight into C. sinensis pathogenesis and could inform therapeutic development against human clonorchiasis. Further research is warranted to elucidate the underlying mechanisms driving these changes and their implications for host-parasite interactions.


Title: L'infection par Clonorchis sinensis induit des changements pathologiques dans l'épithélium des voies biliaires félines et modifie la composition du microbiote biliaire. Abstract: Contexte : Clonorchis sinensis est une douve zoonotique du foie qui habite les voies biliaires du foie humain pendant des périodes prolongées, conduisant au cholangiocarcinome. Des recherches récentes indiquent des associations entre une altération du microbiote biliaire et des pathologies des voies biliaires. Cependant, les impacts de l'infection par C. sinensis sur l'épithélium des voies biliaires et les effets ultérieurs sur le microbiote biliaire restent inconnus. Méthodes : Des échantillons de voies biliaires félines ont été prélevés sur des chats non infectés et infectés par C. sinensis. Un examen histopathologique a été réalisé pour évaluer les modifications épithéliales, la fibrose, la mucine et la prolifération cellulaire à l'aide de la coloration à l'hématoxyline-éosine et de l'immunohistochimie. De plus, la composition du microbiote biliaire a été analysée par séquençage du gène de l'ARNr 16S. Des analyses statistiques ont été menées pour comparer la diversité microbienne et l'abondance relative entre les échantillons infectés et non infectés. Résultats : L'analyse histopathologique des voies biliaires félines infectées a révélé une hyperplasie épithéliale importante caractérisée par une prolifération cellulaire accrue. De plus, une fibrose péricanalaire et une fibrose du collagène ont été observées dans les échantillons infectés par rapport aux témoins non infectés. La richesse microbienne biliaire diminue avec la progression de la maladie par rapport aux témoins non infectés. L'abondance des streptocoques est positivement corrélée à la gravité de la maladie, dominant les communautés dans les échantillons avec cancer. L'analyse fonctionnelle prédictive suggère que C. sinensis pourrait favoriser les lésions des voies biliaires en augmentant les gènes microbiens pour le métabolisme des glucides, la réplication et la réparation. Conclusions : Cette étude fournit des informations complètes sur les effets pathologiques de l'infection à C. sinensis sur l'épithélium des voies biliaires félines et son influence sur la composition du microbiote biliaire. Ces nouvelles découvertes donnent un aperçu sur la pathogenèse de C. sinensis et pourraient éclairer le développement thérapeutique contre la clonorchiase humaine. Des recherches supplémentaires sont nécessaires pour élucider les mécanismes sous-jacents à l'origine de ces changements et leurs implications sur les interactions hôte-parasite.


Assuntos
Ductos Biliares , Doenças do Gato , Clonorquíase , Clonorchis sinensis , Microbiota , RNA Ribossômico 16S , Animais , Gatos , Clonorquíase/parasitologia , Clonorquíase/veterinária , Clonorchis sinensis/fisiologia , Ductos Biliares/parasitologia , Ductos Biliares/patologia , Doenças do Gato/parasitologia , Doenças do Gato/microbiologia , RNA Ribossômico 16S/genética , Epitélio/microbiologia , Epitélio/patologia , Fibrose , Proliferação de Células , Masculino
3.
J Vis Exp ; (210)2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39221930

RESUMO

The ovarian surface epithelium (OSE), the outermost layer of the ovary, undergoes rupture during each ovulation and plays a crucial role in ovarian wound healing while restoring ovarian integrity. Additionally, the OSE may serve as the source of epithelial ovarian cancers. Although the OSE regenerative properties have been well studied in mice, understanding the precise mechanism of tissue repair in the human ovary remains hampered by limited access to human ovaries and suitable in vitro culture protocols. Tissue-specific organoids, miniaturized in vitro models replicating both structural and functional aspects of the original organ, offer new opportunities for studying organ physiology, disease modeling, and drug testing. Here, we describe a method to isolate primary human OSE (hOSE) from whole ovaries and establish hOSE organoids. We include a morphological and cellular characterization showing heterogeneity between donors. Additionally, we demonstrate the capacity of this culture method to evaluate hormonal effects on OSE-organoid growth over a 2-week period. This method may enable the discovery of factors contributing to OSE regeneration and facilitate patient-specific drug screenings for malignant OSE.


Assuntos
Organoides , Ovário , Regeneração , Humanos , Organoides/citologia , Feminino , Ovário/citologia , Ovário/fisiologia , Regeneração/fisiologia , Epitélio/fisiologia
4.
Cells ; 13(17)2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39272975

RESUMO

Ciliated epithelia are widespread in animals and play crucial roles in many developmental and physiological processes. Epithelia composed of multi-ciliated cells allow for directional fluid flow in the trachea, oviduct and brain cavities. Monociliated epithelia play crucial roles in vertebrate embryos, from the establishment of left-right asymmetry to the control of axis curvature via cerebrospinal flow motility in zebrafish. Cilia also have a central role in the motility and feeding of free-swimming larvae in a variety of marine organisms. These diverse functions rely on the coordinated orientation (rotational polarity) and asymmetric localization (translational polarity) of cilia and of their centriole-derived basal bodies across the epithelium, both being forms of planar cell polarity (PCP). Here, we review our current knowledge on the mechanisms of the translational polarity of basal bodies in vertebrate monociliated epithelia from the molecule to the whole organism. We highlight the importance of live imaging for understanding the dynamics of centriole polarization. We review the roles of core PCP pathways and of apicobasal polarity proteins, such as Par3, whose central function in this process has been recently uncovered. Finally, we emphasize the importance of the coordination between polarity proteins, the cytoskeleton and the basal body itself in this highly dynamic process.


Assuntos
Polaridade Celular , Centríolos , Cílios , Animais , Cílios/metabolismo , Cílios/fisiologia , Centríolos/metabolismo , Epitélio/metabolismo , Epitélio/fisiologia , Humanos , Células Epiteliais/metabolismo , Células Epiteliais/citologia , Corpos Basais/metabolismo
5.
Pathol Res Pract ; 262: 155538, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39191196

RESUMO

The mesothelium is a non-adhesive protective surface that lines the serosal cavities and organs within the body. The glycocalyx is a complex structure that coats the outer layer of the mesothelium. However, due to the limitations of conventional fixation techniques, studies on glycans are limited. In this study, lectin staining of frozen tissues was performed to investigate the diversity of glycans in the glycocalyx of mesothelial cells in mice. Datura stramonium lectin (DSL), which recognizes lactosamine and binds to Galectin-3 and -1, was broadly bound to the mesothelial cells of the visceral and parietal peritoneum but not to the pancreas, liver, intestine, or heart. Furthermore, human mesothelial cells in the omentum and parietal peritoneum were positive for DSL. Erythrina cristagalli lectin binding was specific to mesothelial cells in the parietal peritoneum, that is, the pleura, diaphragm, and peritoneum. Intriguingly, surface sialylation, the key element in reducing peritoneal dissemination and implantation, and promoting ascites formation by ovarian carcinoma cells, was much higher in the parietal peritoneum than in the omentum. These findings revealed slight differences in the glycans of mesothelial cells of different organs, which may be related to clinical diseases. These results also suggest that there may be differences in the functions of parietal and visceral mesothelial cells.


Assuntos
Glicocálix , Lectinas , Glicocálix/metabolismo , Animais , Camundongos , Lectinas/metabolismo , Epitélio/metabolismo , Humanos , Peritônio/metabolismo , Peritônio/patologia , Feminino , Coloração e Rotulagem/métodos , Omento/metabolismo , Omento/patologia
6.
In Vivo ; 38(5): 2294-2299, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39187341

RESUMO

BACKGROUND/AIM: Cigarette smoke has been shown to induce a phenotype in humans known as "acquired cystic fibrosis". This occurs because the cystic fibrosis transmembrane conductance regulator (CFTR) functions are impaired systemically due to the deleterious effects of smoke components. Elucidation of cigarette smoke effects on the tracheal epithelium is important. The aim of this study was to develop an ex vivo sheep tracheal model to investigate tracheal ion function. In this model, the epithelial sodium channel (ENaC) is inhibited after exposure to cigarette smoke extract (CSE) as a proof of principle. MATERIALS AND METHODS: Tracheas were isolated from healthy sheep and the tracheal epithelium was surgically excised. Tissues were mounted in Ussing chambers and the short circuit current (Isc) was measured after incubation with 5% CSE in PBS or PBS alone for 30 min. The function of ENaC was investigated by the addition of amiloride (10-5M) apically. Western blot analysis was performed to assess differences in ENaC quantity after CSE exposure. Some specimens were stained with H&E for detection of histological alterations. RESULTS: The amiloride effect on normal epithelium led to a significant decrease in Isc [ΔI=33±5.92 µA/cm2; p<0.001 versus control experiments (ΔI=1.44±0.71 µA/cm2)]. After incubation with CSE, ENaC Isc was significantly reduced (ΔI=14.80±1.96 µA/cm2; p<0.001). No differences in αENaC expression were observed between CSE-exposed and normal tracheal epithelium. Histological images post CSE incubation revealed decreases in the height of the epithelium, with basal cell hyperplasia and loss of ciliated cells. CONCLUSION: Reduced ENaC inhibition by amiloride after CSE incubation could be due to alterations in the tracheal epithelium.


Assuntos
Canais Epiteliais de Sódio , Traqueia , Animais , Canais Epiteliais de Sódio/metabolismo , Ovinos , Traqueia/metabolismo , Traqueia/efeitos dos fármacos , Traqueia/patologia , Projetos Piloto , Fumaça/efeitos adversos , Amilorida/farmacologia , Mucosa Respiratória/metabolismo , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/patologia , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Epitélio/patologia
7.
Int J Pediatr Otorhinolaryngol ; 184: 112079, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39173268

RESUMO

OBJECTIVE: In recent years, the clinical efficacy of medications for adenoid hypertrophy has been demonstrated. Topical nasal steroids have effects to shrink hypertrophic adenoids and improve symptoms of associated diseases. However, the mechanism which topical steroid administrations cause adenoid shrinkage remains unclear, herein, sensitivity for topical steroids in the mucosal epithelium of adenoids was evaluated histologically by comparing with tonsils. METHODS: Histological analysis was performed on adenoids and tonsils removed from 32 pediatric patients with adenoid hypertrophy. In hematoxylin-eosin-stained specimens, the morphology of the mucosal epithelium and eosinophil infiltration were evaluated. The expression of the glucocorticoid receptor (GR), interleukin (IL)-4, and IL-25 in the mucosal epithelium was evaluated, and the staining intensity was scored as 0 (none), 1 (weak), and 2 (strong). The number of eosinophils and expression scores of GR, IL-4, and IL-25 were statistically compared between adenoids and tonsils and analyzed correlations with adenoids sizes. RESULTS: Adenoids were covered with ciliated epithelium, and eosinophils in the mucosal epithelium and submucosal area was higher than tonsils (p < 0.05). GR expression in the most superficial layer of the mucosal epithelium was observed in adenoids, and the expression intensity score was higher than that in tonsils (p < 0.05). IL-4 and IL-25 were more widely expressed in the mucosal epithelium of adenoids than in tonsils, and their expression intensity scores were also higher than in tonsils (p < 0.05). A correlation was found between adenoid size and the intensity of IL-25 expression in the adenoid epithelium (p < 0.05). CONCLUSION: Eosinophilic inflammations in adenoids mucosal epithelium could be one of etiology of adenoid hypertrophy, and the GR and eosinophilic inflammation in the adenoids mucosal epithelium might be target of topical nasal steroids to shrink hypertrophic adenoids.


Assuntos
Tonsila Faríngea , Eosinófilos , Hipertrofia , Tonsila Palatina , Receptores de Glucocorticoides , Humanos , Tonsila Faríngea/patologia , Tonsila Faríngea/metabolismo , Receptores de Glucocorticoides/metabolismo , Masculino , Criança , Feminino , Eosinófilos/metabolismo , Pré-Escolar , Tonsila Palatina/patologia , Interleucina-17/metabolismo , Mucosa/patologia , Mucosa/metabolismo , Interleucina-4/metabolismo , Epitélio/patologia , Epitélio/metabolismo , Glucocorticoides , Citocinas/metabolismo , Adolescente
8.
Nature ; 632(8025): 647-655, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39112699

RESUMO

Biomolecular condensates enable cell compartmentalization by acting as membraneless organelles1. How cells control the interactions of condensates with other cellular structures such as membranes to drive morphological transitions remains poorly understood. We discovered that formation of a tight-junction belt, which is essential for sealing epithelial tissues, is driven by a wetting phenomenon that promotes the growth of a condensed ZO-1 layer2 around the apical membrane interface. Using temporal proximity proteomics in combination with imaging and thermodynamic theory, we found that the polarity protein PATJ mediates a transition of ZO-1 into a condensed surface layer that elongates around the apical interface. In line with the experimental observations, our theory of condensate growth shows that the speed of elongation depends on the binding affinity of ZO-1 to the apical interface and is constant. Here, using PATJ mutations, we show that ZO-1 interface binding is necessary and sufficient for tight-junction belt formation. Our results demonstrate how cells exploit the collective biophysical properties of protein condensates at membrane interfaces to shape mesoscale structures.


Assuntos
Condensados Biomoleculares , Membrana Celular , Junções Íntimas , Molhabilidade , Animais , Cães , Humanos , Condensados Biomoleculares/metabolismo , Condensados Biomoleculares/química , Compartimento Celular , Membrana Celular/metabolismo , Membrana Celular/química , Epitélio , Células HEK293 , Células Madin Darby de Rim Canino , Mutação , Ligação Proteica , Termodinâmica , Proteínas de Junções Íntimas/metabolismo , Junções Íntimas/metabolismo , Junções Íntimas/química , Proteína da Zônula de Oclusão-1/genética , Proteína da Zônula de Oclusão-1/metabolismo , Proteômica
9.
Dev Biol ; 516: 221-236, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39154741

RESUMO

Sharks and their relatives are typically covered in highly specialized epithelial appendages embedded in the skin called dermal denticles; ancient tooth-like units (odontodes) composed of dentine and enamel-like tissues. These 'skin teeth' are remarkably similar to oral teeth of vertebrates and share comparable morphological and genetic signatures. Here we review the histological and morphological data from embryonic sharks to uncover characters that unite all tooth-like elements (odontodes), including teeth and skin denticles in sharks. In addition, we review the differences between the skin and oral odontodes that reflect their varied capacity for renewal. Our observations have begun to decipher the developmental and genetic shifts that separate these seemingly similar dental units, including elements of the regenerative nature in both oral teeth and the emerging skin denticles from the small-spotted catshark (Scyliorhinus canicula) and other chondrichthyan models. Ultimately, we ask what defines a tooth at both the molecular and morphological level. These insights aim to help us understand how nature makes, replaces and evolves a vast array of odontodes.


Assuntos
Evolução Biológica , Regeneração , Tubarões , Dente , Animais , Tubarões/embriologia , Tubarões/fisiologia , Dente/embriologia , Regeneração/fisiologia , Epitélio/embriologia , Pele/embriologia , Odontogênese/fisiologia
10.
Dev Biol ; 516: 207-220, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39181419

RESUMO

Larvacean tunicates feature a spectacular innovation not seen in other animals - the trunk oikoplastic epithelium (OE). This epithelium produces a house, a large and complex extracellular structure used for filtering and concentrating food particles. Previously we identified several homeobox transcription factor genes expressed during early OE patterning. Among these are two Pax3/7 copies that we named pax37A and pax37B. The vertebrate homologs, PAX3 and PAX7 are involved in developmental processes related to neural crest and muscles. In the ascidian tunicate Ciona intestinalis, Pax3/7 plays a role in the development of cells deriving from the neural plate border, including trunk epidermal sensory neurons and tail nerve cord neurons, as well as in the neural tube closure. Here we have investigated the roles of Oikopleura dioica pax37A and pax37B in the development of the OE, by using CRISPR-Cas9 mutant lines and analyzing scRNA-seq data from wild-type animals. We found that pax37B but not pax37A is essential for the differentiation of cell fields that produce the food concentrating filter of the house: the anterior Fol, giant Fol and Nasse cells. Trajectory analysis supported a neuroepithelial-like or a preplacodal ectoderm transcriptional signature in these cells. We propose that the highly specialized secretory epithelial cells of the Fol region either maintained or evolved neuroepithelial features. This is supported by a fragmented gene regulatory network involved in their development that also operates in ascidian epidermal neurons.


Assuntos
Fator de Transcrição PAX3 , Fator de Transcrição PAX7 , Urocordados , Animais , Urocordados/embriologia , Urocordados/genética , Fator de Transcrição PAX7/genética , Fator de Transcrição PAX7/metabolismo , Fator de Transcrição PAX3/genética , Fator de Transcrição PAX3/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Epitélio/metabolismo , Ciona intestinalis/genética , Ciona intestinalis/embriologia , Diferenciação Celular/genética , Crista Neural/metabolismo , Crista Neural/embriologia
11.
Cell Rep ; 43(8): 114589, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39110589

RESUMO

Caspase recruitment domain family member 14 (CARD14) and its variants are associated with both atopic dermatitis (AD) and psoriasis, but their mechanistic impact on skin barrier homeostasis is largely unknown. CARD14 is known to signal via NF-κB; however, CARD14-NF-κB signaling does not fully explain the heterogeneity of CARD14-driven disease. Here, we describe a direct interaction between CARD14 and MYC and show that CARD14 signals through MYC in keratinocytes to coordinate skin barrier homeostasis. CARD14 directly binds MYC and influences barrier formation in an MYC-dependent fashion, and this mechanism is undermined by disease-associated CARD14 variants. These studies establish a paradigm that CARD14 activation regulates skin barrier function by two distinct mechanisms, including activating NF-κB to bolster the antimicrobial (chemical) barrier and stimulating MYC to bolster the physical barrier. Finally, we show that CARD14-dependent MYC signaling occurs in other epithelia, expanding the impact of our findings beyond the skin.


Assuntos
Proteínas Adaptadoras de Sinalização CARD , Epiderme , Homeostase , Queratinócitos , NF-kappa B , Proteínas Proto-Oncogênicas c-myc , Humanos , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Proteínas Adaptadoras de Sinalização CARD/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Epiderme/metabolismo , Queratinócitos/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais , Dermatite Atópica/metabolismo , Dermatite Atópica/patologia , Dermatite Atópica/genética , Guanilato Ciclase/metabolismo , Guanilato Ciclase/genética , Epitélio/metabolismo , Ligação Proteica , Psoríase/metabolismo , Psoríase/genética , Psoríase/patologia , Proteínas de Membrana
12.
Tissue Cell ; 90: 102514, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39121582

RESUMO

The vocal folds vibrate to produce voice, undergoing significant stress due to contact and shearing force. The epithelium operates as the primary protective layer of the tissue against stress and vibratory damage, as well as to provide a barrier against foreign organisms and toxins. Within the vocal fold epithelium, non-epithelial cells were identified that may interrupt the epithelium and compromise the epithelial barrier's protective function. Human vocal fold samples with a variety of pathologies were compared to normal vocal folds. Analysis included the number of cells in the epithelium and epithelial thickness. Vocal fold sections from 10 human tissue samples were assessed via H&E staining and immunofluorescent co-labeling. Three cell populations (vimentin expressing, CD-45 expressing, and cells expressing both) were identified within the epithelium. Statistical analysis revealed that the abnormal samples had a significantly greater number of vimentin-positive cells/area within the epithelium compared to the normal samples. Additionally, normal tissue samples had a significantly greater epithelial depth, suggesting a more robust epithelial barrier compared to tissue with pathology. Knowledge of the function of these cells could lead to a better understanding of how the local immune environment near and within vocal fold epithelium changes in the presence of different pathologies.


Assuntos
Prega Vocal , Prega Vocal/citologia , Prega Vocal/metabolismo , Humanos , Células Epiteliais/metabolismo , Células Epiteliais/citologia , Masculino , Epitélio/metabolismo , Feminino , Vimentina/metabolismo , Pessoa de Meia-Idade
13.
Nat Commun ; 15(1): 7118, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39160171

RESUMO

Although epithelial folding is commonly studied using in vivo animal models, such models exhibit critical limitations in terms of real-time observation and independent control of experimental parameters. Here, we develop a tissue-scale in vitro epithelial bilayer folding model that incorporates an epithelium and extracellular matrix (ECM) hydrogel, thereby emulating various folding structures found in in vivo epithelial tissue. Beyond mere folding, our in vitro model realizes a hierarchical transition in the epithelial bilayer, shifting from periodic wrinkles to a single deep fold under compression. Experimental and theoretical investigations of the in vitro model imply that both the strain-stiffening of epithelium and the poroelasticity of ECM influence the folded structures of epithelial tissue. The proposed in vitro model will aid in investigating the underlying mechanism of tissue-scale in vivo epithelial folding relevant to developmental biology and tissue engineering.


Assuntos
Células Epiteliais , Matriz Extracelular , Hidrogéis , Matriz Extracelular/metabolismo , Animais , Epitélio/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/citologia , Hidrogéis/química , Engenharia Tecidual/métodos , Humanos , Modelos Biológicos , Células Madin Darby de Rim Canino , Cães , Elasticidade
14.
Nat Commun ; 15(1): 7145, 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39164270

RESUMO

The existence and function of Lgr5+ cells within the developing esophagus remains unknown. Here, we document multiple discrete Lgr5+ populations in the developing mouse esophagus, predominantly within nascent epithelial and external muscle layers. Lgr5 expression initially emerges in the developing proximal embryonic epithelium, but progressively extends distally and persists within the distal epithelium of neonates. Fate mapping and ablation analyses reveal a long-term contribution of epithelial Lgr5+ cells to esophageal organogenesis. Additionally, Lgr5-expressing cells are present in the developing external muscle layer, particularly during the development of the striated component. Fate mapping reveals a significant contribution of these embryonic Lgr5+ cells to the adult muscle layer. Embryonic Lgr5+ epithelial cells are also found to be important for regulating epithelial development, serving as a key source of Wnt6, among other ligands, to promote epithelial cell proliferation and formation of epithelial layers. These findings significantly enhance our understanding of esophageal development and shed light on the involvement of Lgr5+ stem/progenitor cells during organogenesis. Importantly, this study lays the foundation for investigating esophageal diseases related to the Lgr5+ stem/progenitor cell pool.


Assuntos
Células Epiteliais , Esôfago , Desenvolvimento Muscular , Receptores Acoplados a Proteínas G , Células-Tronco , Animais , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Esôfago/citologia , Esôfago/metabolismo , Esôfago/embriologia , Camundongos , Células-Tronco/metabolismo , Células-Tronco/citologia , Células Epiteliais/metabolismo , Células Epiteliais/citologia , Proliferação de Células , Organogênese , Epitélio/metabolismo , Epitélio/embriologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Diferenciação Celular
15.
Sci Rep ; 14(1): 18644, 2024 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-39128895

RESUMO

To accurately measure the vaginal mucosa thickness across different age groups using histopathologic techniques and investigate the factors that may influence the thickness changes. This study aims to provide clinicians with objective evidence of variations in vaginal mucosal thickness, facilitating personalized medical decisions for patients. A retrospective analysis was conducted on clinical data from 348 patients who underwent local vaginal wall resection at the West China Second University Hospital, Sichuan University, from January 2021 and May 2022. The thickness of vaginal mucosa, epithelium and lamina propria was measured precisely under the microscope. And the 10th, 25th, 50th, 75th, and 90th percentile values of vaginal mucosa thickness across different age groups were counted and charted a dot-line plot. The percentile values for vaginal mucosa thickness exhibited a decreasing trend with increasing age; vaginal mucosa thickness showed significant correlations with times of delivery (P = 0.031) and age (P < 0.001), both of which were negatively associated. And vaginal mucosa thickness demonstrated no significant correlation with body mass index (BMI) (P = 0.325), times of abortions (P = 0.511), times of gestation (P = 0.101), menstrual cycle (P = 0.533), or types of delivery (P = 0.056); epithelial thickness showed significant associations with age (P < 0.001) and types of delivery (P = 0.017), both of which were negative correlations. Moreover, BMI (P = 0.429), times of abortions (P = 0.764), delivery (P = 0.079), gestation (P = 0.475), and menstrual cycle (P = 0.950) were nonassociated with epithelial thickness; lamina propria thickness displayed a significant correlation only with age (P = 0.002), and there were no obvious correlations observed between lamina propria thickness and BMI (P = 0.374), times of abortion (P = 0.417), delivery (P = 0.053), gestation (P = 0.101), types of delivery (P = 0.132) and menstrual cycle (P = 0.495). Moreover, when the age segmentation was thresholded at 35 and 50 years, both epithelial thickness and vaginal mucosa thickness were significantly correlated with age (P < 0.05). Lamina propria thickness was associated with age when the age threshold was set at 35 years (P = 0.007), whereas it showed no strong link with age when the age threshold was 50 years (P = 0.072). This study has innovatively established percentile reference values for vaginal mucosa thickness based on histopathology, furnishing clinicians with objective evidence of variations in vaginal mucosal thickness to facilitate personalized medical decisions for patients. The findings demonstrated a strong link between vaginal mucosa thickness and age, with epithelium likely playing a predominant role, while the association with lamina propria appeared to be less significant. Further research involving a larger sample size is warranted to elucidate the potential relationship with the lamina propria.


Assuntos
Mucosa , Vagina , Humanos , Feminino , Vagina/patologia , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Mucosa/patologia , Adulto Jovem , Idoso , China , Fatores Etários , Adolescente , Índice de Massa Corporal , Epitélio/patologia
16.
Exp Cell Res ; 441(1): 114155, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39002689

RESUMO

At least one-third of patients with epithelial ovarian cancer (OC) present ascites at diagnosis and almost all have ascites at recurrence especially because of the propensity of the OC cells to spread in the abdominal cavity leading to peritoneal metastasis. The influence of ascites on the development of pre-metastatic niches, and on the biological mechanisms leading to cancer cell colonization of the mesothelium, remains poorly understood. Here, we show that ascites weakens the mesothelium by affecting the morphology of mesothelial cells and by destabilizing their distribution in the cell cycle. Ascites also causes destabilization of the integrity of mesothelium by modifying the organization of cell junctions, but it does not affect the synthesis of N-cadherin and ZO-1 by mesothelial cells. Moreover, ascites induces disorganization of focal contacts and causes actin cytoskeletal reorganization potentially dependent on the activity of Rac1. Ascites allows the densification and reorganization of ECM proteins of the mesothelium, especially fibrinogen/fibrin, and indicates that it is a source of the fibrinogen and fibrin surrounding OC spheroids. The fibrin in ascites leads to the adhesion of OC spheroids to the mesothelium, and ascites promotes their disaggregation followed by the clearance of mesothelial cells. Both αV and α5ß1 integrins are involved. In conclusion ascites and its fibrinogen/fibrin composition affects the integrity of the mesothelium and promotes the integrin-dependent implantation of OC spheroids in the mesothelium.


Assuntos
Ascite , Fibrina , Fibrinogênio , Integrina alfa5beta1 , Neoplasias Ovarianas , Esferoides Celulares , Microambiente Tumoral , Humanos , Feminino , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Ascite/patologia , Ascite/metabolismo , Integrina alfa5beta1/metabolismo , Esferoides Celulares/metabolismo , Esferoides Celulares/patologia , Fibrinogênio/metabolismo , Fibrina/metabolismo , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/metabolismo , Neoplasias Peritoneais/patologia , Carcinoma Epitelial do Ovário/metabolismo , Carcinoma Epitelial do Ovário/patologia , Linhagem Celular Tumoral , Receptores de Vitronectina/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo , Adesão Celular , Peritônio/patologia , Peritônio/metabolismo , Epitélio/metabolismo , Epitélio/patologia , Caderinas/metabolismo , Células Tumorais Cultivadas
17.
Mol Cell Biol ; 44(8): 334-343, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38975675

RESUMO

Interferon epsilon (IFNε) is a unique type I interferon (IFN) that shows distinct constitutive expression in reproductive tract epithelium. Understanding how IFNε expression is regulated is critical for the mechanism of action in protecting the mucosa from infection. Combined computational and experimental investigation of the promoter of IFNε predicted transcription factor binding sites for the ETS family of transcription factors. We demonstrate here that Ifnε is regulated by Elf3, an epithelial restricted member of the ETS family. It is co-expressed with IFNε at the epithelium of uterus, lung and intestine, and we focused on regulation of IFNε expression in the uterus. Promoter reporter studies demonstrated that Elf3 was a strong driver of Ifnε expression; knockdown of Elf3 reduced expression levels of IFNε; Elf3 regulated Ifnε expression and chromatin immunoprecipitation (ChIP) confirmed the direct binding of Elf3 to the IFNε promoter. These data show that Elf3 is important in regulating protective mucosal immunity by driving constitutive expression of IFNε to protect mucosal tissues from infection in at least three organ systems.


Assuntos
Proteínas de Ligação a DNA , Regiões Promotoras Genéticas , Fatores de Transcrição , Animais , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Regiões Promotoras Genéticas/genética , Feminino , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Camundongos , Humanos , Regulação da Expressão Gênica , Útero/metabolismo , Útero/imunologia , Mucosa/metabolismo , Mucosa/imunologia , Sítios de Ligação , Interferon Tipo I/metabolismo , Camundongos Endogâmicos C57BL , Epitélio/metabolismo , Proteínas Proto-Oncogênicas c-ets/metabolismo , Proteínas Proto-Oncogênicas c-ets/genética , Pulmão/metabolismo , Pulmão/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/imunologia
19.
Ultrastruct Pathol ; 48(5): 438-443, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39078195

RESUMO

Emperipolesis is a cell-within-cell phenomenon distinct from phagocytosis more often described in Rosai-Dorfman disease, where usually lymphocytes or other bone marrow cells (plasma cells, erythroblasts or neutrophils) are entirely surrounded but not engulfed by macrophages as the host cell, but occasionally megakaryocytes and neoplastic could be. Mesothelial cell has been described in a couple of cases of lymphomas affecting serous membranes, but never described in pleuritis. In the present work, the first case of emperipolesis by mesothelial cells in a patient with self-limited pleural effusion was demonstrated by immunohistochemistry and Electron Microscopy studies.


Assuntos
Emperipolese , Histiocitose Sinusal , Humanos , Pessoa de Meia-Idade , Células Epiteliais/patologia , Células Epiteliais/ultraestrutura , Epitélio/patologia , Epitélio/ultraestrutura , Histiocitose Sinusal/patologia , Histiocitose Sinusal/complicações , Imuno-Histoquímica , Derrame Pleural/patologia
20.
Dev Biol ; 515: 60-66, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38964706

RESUMO

Terminal differentiation of epithelial cells is critical for the barrier function of the skin, the growth of skin appendages, such as hair and nails, and the development of the skin of amniotes. Here, we present the hypothesis that the differentiation of cells in the embryonic periderm shares characteristic features with the differentiation of epithelial cells that support the morphogenesis of cornified skin appendages during postnatal life. The periderm prevents aberrant fusion of adjacent epithelial sites during early skin development. It is shed off when keratinocytes of the epidermis form the cornified layer, the stratum corneum. A similar role is played by epithelia that ensheath cornifying skin appendages until they disintegrate to allow the separation of the mature part of the skin appendage from the adjacent tissue. These epithelia, exemplified by the inner root sheath of hair follicles and the epithelia close to the free edge of nails or claws, are referred to as scaffolding epithelia. The periderm and scaffolding epithelia are similar with regard to their transient functions in separating tissues and the conserved expression of trichohyalin and trichohyalin-like genes in mammals and birds. Thus, we propose that parts of the peridermal differentiation program were coopted to a new postnatal function during the evolution of cornified skin appendages in amniotes.


Assuntos
Diferenciação Celular , Diferenciação Celular/fisiologia , Animais , Pele/embriologia , Pele/citologia , Pele/metabolismo , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Epitélio/embriologia , Epitélio/metabolismo , Epiderme/embriologia , Epiderme/metabolismo , Queratinócitos/citologia , Queratinócitos/metabolismo , Folículo Piloso/embriologia , Folículo Piloso/citologia , Humanos , Morfogênese
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