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1.
Cytokine ; 138: 155391, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33302223

RESUMEN

Psoriasis is a common chronic inflammatory dermatitis in which various cytokines play a detrimental role. The cytokine tumor necrosis factor-related weak inducer of apoptosis (TWEAK) is involved in the pathogenesis of multiple inflammatory disorders. However, the potential role of TWEAK in various subtypes of psoriasis has not been studied in depth. To investigate whether the levels of TWEAK are associated with clinical traits and the levels of some known psoriasis-related cytokines, such as interleukin (IL)-17A, IL-22, interferon (IFN)-γ, and IL-36γ, 20 patients with psoriasis vulgaris (PV), 8 patients with pustular psoriasis (PP), 8 patients with erythrodermic psoriasis (EP), and 20 healthy controls (HCs) were recruited into this study. The levels of serum cytokines were detected by commercial enzyme-linked immunosorbent assay kits. The average levels of TWEAK, IL-17A, IL-22, IFN-γ, and IL-36γ were significantly higher in the psoriasis groups than in the HC group. Furthermore, there was a statistically significant correlation between TWEAK and IL-17A/IFN-γ in PV and IL-36γ in EP, but there was no correlation between TWEAK and IL-22 in any subtype of psoriasis. This study suggests that TWEAK may have a role in the pathogenesis of PV, PP, and EP via synergy with IL-17A, IFN-γ, or IL-36γ, but not with IL-22.


Asunto(s)
Citocina TWEAK/biosíntesis , Citocina TWEAK/sangre , Psoriasis/sangre , Psoriasis/metabolismo , Adolescente , Adulto , Anciano , Niño , Citocinas/metabolismo , Femenino , Hospitalización , Humanos , Interferón gamma/biosíntesis , Interleucina-1/biosíntesis , Interleucina-17/biosíntesis , Masculino , Persona de Mediana Edad , Psoriasis/fisiopatología , Adulto Joven
3.
Health Qual Life Outcomes ; 14: 17, 2016 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-26841932

RESUMEN

BACKGROUND: The Dermatology Life Quality Index (DLQI) is the most widely used measure of health-related quality of life (HRQoL) associated with skin disease. Recently, the psychometric properties of the DLQI have caused some controversy because the instrument appears not to meet the requirements of modern test theory. The purpose of this study was to assess whether these psychometric issues also occur in Chinese patients with neurodermatitis. METHODS: One hundred fifty consecutive outpatients (83 males and 67 females) seeking treatment for neurodermatitis were assessed for eligibility for this prospective study between July 1, 2011 and September 30, 2011. The DLQI and a demographic questionnaire were completed. One female participant who incompletely answered the DLQI was excluded. Data were analyzed using the Rasch model in order to obtain meaningful scores for the DLQI. Scale assessment included analysis of rating scale function, item fit to the Rasch model, aspects of person-response validity, unidimensionality, person-separation reliability, and differential item function. RESULTS: The rating scale advanced monotonically for all items in the DLQI, but item 9 did not demonstrate acceptable goodness-of-fit (Infit MnSq values >1.3) to the Rasch model. The 10 items of the DLQI met the criteria for person-separation reliability (PSI = 2.38) and the first latent dimension (general QoL) accounted for 50.8 % of the variance; but the variance explained by the second dimension (7.1 %) exceeded the criterion of 5 %. There were also limitations related to person-response validity, because ≥ 5 % (18.1 %) of cases demonstrated unacceptable fit. There was no uniform differential item functioning. CONCLUSIONS: For neurodermatitis patients, the DLQI seems to have poor fit to the Rasch model; therefore, we recommend against using this instrument with neurodermatitis patients.


Asunto(s)
Adaptación Psicológica , Pueblo Asiatico/psicología , Actitud Frente a la Salud , Neurodermatitis/psicología , Psicometría/instrumentación , Calidad de Vida/psicología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Reproducibilidad de los Resultados , Estrés Psicológico , Encuestas y Cuestionarios , Adulto Joven
4.
Lasers Med Sci ; 31(3): 453-7, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26796708

RESUMEN

We evaluated the short-term and long-term effects of the 1550 nm erbium:glass (Er:glass) fractional laser in the treatment of facial acne vulgaris. Forty-five (9 male and 36 female) acne patients were treated 4 times at 4-week intervals with the following parameters: 169 spot density and 15-30 mJ/cm(2) fluence. There was no control group. The laser spots were adjustable (maximum overlap: 20%) according to the treatment area, and delivered in rows in order to cover all the face. Clinical photographs were taken. The IGA scores and lesion counts were performed for each treatment. Their current state was obtained by phone call follow-up to determine the long-term effect and photographs were offered by themselves or taken in hospital. After four treatments, all patients had an obvious reduction of lesion counts and IGA score and the peak lesion counts decreased to 67.7% after the initial four treatment sessions. For long-term effect, 8 patients lost follow-up, hence 37 patients were followed-up. 8 patients were 2-year follow up, 27 at the 1-year follow-up, and all patients at the half-year follow-up. The mean percent reduction was 72% at the half-year follow-up, 79 at the 1-year follow-up and 75% at the 2-year follow-up. Side effects and complications were limited to transient erythema and edema, and few patients suffered from transient acne flare-ups and sensitivity. All patients responded that their skin was less prone to oiliness. In conclusion, acne can be successfully treated by 1550 nm Er:glass fractional laser, with few side effects and prolonged acne clearing.


Asunto(s)
Acné Vulgar/radioterapia , Láseres de Estado Sólido/uso terapéutico , Terapia por Luz de Baja Intensidad , Adulto , Cara/patología , Cara/efectos de la radiación , Femenino , Estudios de Seguimiento , Humanos , Masculino , Piel/patología , Piel/efectos de la radiación , Resultado del Tratamiento , Adulto Joven
5.
Stem Cell Res Ther ; 13(1): 270, 2022 06 21.
Artículo en Inglés | MEDLINE | ID: mdl-35729659

RESUMEN

Stem and progenitor cells (SPCs) possess self-remodeling ability and differentiation potential and are responsible for the regeneration and development of organs and tissue systems. However, the precise mechanisms underlying the regulation of SPC biology remain unclear. Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) acts on miscellaneous cells via binding to fibroblast growth factor-inducible 14 (Fn14) and exerts pleiotropic functions in the regulation of divergent stem cell fates. TWEAK/Fn14 signaling can regulate the proliferation, differentiation, and migration of multiple SPCs as well as tumorigenesis in certain contexts. Although TWEAK's roles in modulating multiple SPCs are sparsely reported, the systemic effector functions of this multifaceted protein have not been fully elucidated. In this review, we summarized the fate decisions of TWEAK/Fn14 signaling on multiple stem cells and characterized its potential in stem cell therapy.


Asunto(s)
Receptores del Factor de Necrosis Tumoral , Transducción de Señal , Receptores del Factor de Necrosis Tumoral/genética , Receptores del Factor de Necrosis Tumoral/metabolismo , Transducción de Señal/fisiología , Células Madre/metabolismo , Receptor de TWEAK/genética , Receptor de TWEAK/metabolismo , Factor de Necrosis Tumoral alfa
6.
Front Immunol ; 13: 1039618, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36618396

RESUMEN

Hepatopulmonary syndrome (HPS) is a serious pulmonary vascular complication that causes respiratory insufficiency in patients with chronic liver diseases. HPS is characterized by two central pathogenic features-intrapulmonary vascular dilatation (IPVD) and angiogenesis. Endothelial glycocalyx (eGCX) is a gel-like layer covering the luminal surface of blood vessels which is involved in a variety of physiological and pathophysiological processes including controlling vascular tone and angiogenesis. In terms of lung disorders, it has been well established that eGCX contributes to dysregulated vascular contraction and impaired blood-gas barrier and fluid clearance, and thus might underlie the pathogenesis of HPS. Additionally, pharmacological interventions targeting eGCX are dramatically on the rise. In this review, we aim to elucidate the potential role of eGCX in IPVD and angiogenesis and describe the possible degradation-reconstitution equilibrium of eGCX during HPS through a highlight of recent literature. These studies strongly underscore the therapeutic rationale in targeting eGCX for the treatment of HPS.


Asunto(s)
Síndrome Hepatopulmonar , Humanos , Síndrome Hepatopulmonar/etiología , Síndrome Hepatopulmonar/patología , Glicocálix/patología , Pulmón/patología , Vasodilatación , Ligadura
7.
Front Immunol ; 13: 842651, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35958578

RESUMEN

Identifying genetic variation underlying human diseases establishes targets for therapeutic development and helps tailor treatments to individual patients. Large-scale transcriptomic profiling has extended the study of such molecular heterogeneity between patients to somatic tissues. However, the lower resolution of bulk RNA profiling, especially in a complex, composite tissue such as the skin, has limited its success. Here we demonstrate approaches to interrogate patient-level molecular variance in a chronic skin inflammatory disease, psoriasis vulgaris, leveraging single-cell RNA-sequencing of CD45+ cells isolated from active lesions. Highly psoriasis-specific transcriptional abnormalities display greater than average inter-individual variance, nominating them as potential sources of clinical heterogeneity. We find that one of these chemokines, CXCL13, demonstrates significant correlation with severity of lesions within our patient series. Our analyses also establish that genes elevated in psoriatic skin-resident memory T cells are enriched for programs orchestrating chromatin and CDC42-dependent cytoskeleton remodeling, specific components of which are distinctly correlated with and against Th17 identity on a single-cell level. Collectively, these analyses describe systematic means to dissect cell type- and patient-level differences in cutaneous psoriasis using high-resolution transcriptional profiles of human inflammatory disease.


Asunto(s)
Psoriasis , Transcriptoma , Humanos , Psoriasis/patología , ARN , Piel/patología , Células Th17/patología
8.
Sci Immunol ; 7(70): eabl9165, 2022 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-35427179

RESUMEN

Inflammatory conditions represent the largest class of chronic skin disease, but the molecular dysregulation underlying many individual cases remains unclear. Single-cell RNA sequencing (scRNA-seq) has increased precision in dissecting the complex mixture of immune and stromal cell perturbations in inflammatory skin disease states. We single-cell-profiled CD45+ immune cell transcriptomes from skin samples of 31 patients (7 atopic dermatitis, 8 psoriasis vulgaris, 2 lichen planus (LP), 1 bullous pemphigoid (BP), 6 clinical/histopathologically indeterminate rashes, and 7 healthy controls). Our data revealed active proliferative expansion of the Treg and Trm components and universal T cell exhaustion in human rashes, with a relative attenuation of antigen-presenting cells. Skin-resident memory T cells showed the greatest transcriptional dysregulation in both atopic dermatitis and psoriasis, whereas atopic dermatitis also demonstrated recurrent abnormalities in ILC and CD8+ cytotoxic lymphocytes. Transcript signatures differentiating these rash types included genes previously implicated in T helper cell (TH2)/TH17 diatheses, segregated in unbiased functional networks, and accurately identified disease class in untrained validation data sets. These gene signatures were able to classify clinicopathologically ambiguous rashes with diagnoses consistent with therapeutic response. Thus, we have defined major classes of human inflammatory skin disease at the molecular level and described a quantitative method to classify indeterminate instances of pathologic inflammation. To make this approach accessible to the scientific community, we created a proof-of-principle web interface (RashX), where scientists and clinicians can visualize their patient-level rash scRNA-seq-derived data in the context of our TH2/TH17 transcriptional framework.


Asunto(s)
Dermatitis Atópica , Exantema , Psoriasis , Enfermedades de la Piel , Exantema/metabolismo , Exantema/patología , Humanos , Piel , Enfermedades de la Piel/metabolismo , Enfermedades de la Piel/patología
9.
Cell Rep Med ; 3(8): 100715, 2022 08 16.
Artículo en Inglés | MEDLINE | ID: mdl-35977472

RESUMEN

The homeostatic mechanisms that fail to restrain chronic tissue inflammation in diseases, such as psoriasis vulgaris, remain incompletely understood. We profiled transcriptomes and epitopes of single psoriatic and normal skin-resident T cells, revealing a gradated transcriptional program of coordinately regulated inflammation-suppressive genes. This program, which is sharply suppressed in lesional skin, strikingly restricts Th17/Tc17 cytokine and other inflammatory mediators on the single-cell level. CRISPR-based deactivation of two core components of this inflammation-suppressive program, ZFP36L2 and ZFP36, replicates the interleukin-17A (IL-17A), granulocyte macrophage-colony-stimulating factor (GM-CSF), and interferon gamma (IFNγ) elevation in psoriatic memory T cells deficient in these transcripts, functionally validating their influence. Combinatoric expression analysis indicates the suppression of specific inflammatory mediators by individual program members. Finally, we find that therapeutic IL-23 blockade reduces Th17/Tc17 cell frequency in lesional skin but fails to normalize this inflammatory-suppressive program, suggesting how treated lesions may be primed for recurrence after withdrawal of treatment.


Asunto(s)
Células T de Memoria , Células Th17 , Humanos , Inflamación/metabolismo , Mediadores de Inflamación/metabolismo , Piel/metabolismo
10.
Aging (Albany NY) ; 13(11): 15523-15537, 2021 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-34099591

RESUMEN

S100 calcium-binding protein A8 (S100A8) and S100A9 are small molecular weight calcium-binding regulatory proteins that have been involved in multiple chronic inflammatory diseases. However, the role of S100A8 and S100A9 in keratinocytes in wounded skin and how they are regulated during this process are still unclear. Here, we found that S100A8 and S100A9 were both upregulated in burn-wounded skins in vivo and thermal-stimulated epidermal keratinocytes in vitro, accompanied by increased levels of epithelial-mesenchymal transition (EMT). Then, we demonstrated that upregulation of S100A8 and S100A9 alone or together enhanced characteristics of EMT in normal keratinocytes, manifested by excessive proliferation rate, abnormal ability of cell invasion, and high expression levels of EMT marker proteins. The transcription factor PU box-binding protein (PU.1) bound to the promoter regions and transcriptionally promoted the expression of S100A8 and S100A9 both in the human and mice, and it had strong positive correlations with both S100A8 and S100A9 protein levels in burned skin in vivo. Moreover, PU.1 positively regulated expression of S100A8 and S100A9 in a dose-dependent manner, and enhanced EMT of keratinocytes in vitro. Finally, through the burn mouse model, we found that PU.1-/- mice displayed a lower ability of scar formation, manifested by smaller scar volume, thickness, and collagen content, which could be enhanced by S100A8 and S100A9. In conclusion, PU.1 transcriptionally promotes expression of S100A8 and S100A9, thus positively regulating epithelial-mesenchymal transformation (EMT) and invasive growth of dermal keratinocytes during scar formation post burn.


Asunto(s)
Quemaduras/patología , Calgranulina A/metabolismo , Calgranulina B/metabolismo , Movimiento Celular , Cicatriz/patología , Transición Epitelial-Mesenquimal , Queratinocitos/patología , Proteínas Proto-Oncogénicas/metabolismo , Transactivadores/metabolismo , Adulto , Animales , Proliferación Celular , Modelos Animales de Enfermedad , Femenino , Calor , Humanos , Masculino , Ratones Endogámicos BALB C , Regulación hacia Arriba/genética
11.
Sci Rep ; 11(1): 17746, 2021 09 07.
Artículo en Inglés | MEDLINE | ID: mdl-34493780

RESUMEN

Bullous pemphigoid (BP), the most frequent blistering dermatosis in the elderly, is associated with increased mortality. The severity of BP can be assessed by detecting the anti-BP180 immunoglobulin G (IgG) concentration, but the lab test is not available in many community clinics. BP patients are usually in a hypercoagulable state with increased levels of D-dimer and fibrin degradation products (FDPs). We aimed to evaluate the use of D-dimer and FDPs in assessing BP severity. We compared the levels of plasma D-dimer, plasma FDPs, eosinophil counts, eosinophil cationic protein, and serum anti-BP180 IgG concentration between 48 typical BP patients and 33 Herpes zoster (HZ) patients (control group). Correlational analyses were conducted to determine the relationships between the lab values and common BP severity markers. The plasma D-dimer and FDP levels were higher in BP patients than in HZ controls (D-dimer: 3297 ± 2517 µg/L vs. 569.70 ± 412.40 µg/L; FDP: 9.74 ± 5.88 mg/L vs. 2.02 ± 1.69 mg/L, respectively, P < 0.0001). Significant positive correlations were found between D-dimer/FDP levels and BP severity markers (i.e. anti-BP180 IgG concentration [D-dimer: r = 0.3928, P = 0.0058; FDP: r = 0.4379, P = 0.0019] and eosinophil counts [D-dimer: r = 0.3625, P = 0.0013; FDP: r = 0.2880, P = 0.0472]) in BP patients. We also found an association between FDP and urticaria/erythema lesions (r = 0.3016, P = 0.0372), but no other BPDAI components. In 19 BP patients with complete remission after systemic glucocorticoid treatment, D-dimer and FDP levels decreased post-therapy (D-dimer: 5559 ± 7492 µg/L vs. 1738 ± 1478 µg/L; P < 0.0001; FDP: 11.20 ± 5.88 mg/L vs. 5.13 ± 3.44 mg/L; P = 0.0003), whereas they did not in BP patients with treatment resistant. Plasma D-dimer and FDP are convenient markers to evaluate BP severity assistant on BPDAI and eosinophil counts. FDP is also helpful for inflammatory lesions in BP patients.


Asunto(s)
Productos de Degradación de Fibrina-Fibrinógeno/análisis , Penfigoide Ampolloso/sangre , Anciano , Anciano de 80 o más Años , Autoanticuerpos/sangre , Autoantígenos/inmunología , Biomarcadores , Estudios Transversales , Proteína Catiónica del Eosinófilo/sangre , Eosinofilia/sangre , Eosinofilia/etiología , Femenino , Herpes Zóster/sangre , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Masculino , Persona de Mediana Edad , Colágenos no Fibrilares/inmunología , Penfigoide Ampolloso/complicaciones , Índice de Severidad de la Enfermedad , Trombofilia/sangre , Trombofilia/etiología , Urticaria/sangre , Colágeno Tipo XVII
12.
Phys Rev E ; 102(1-1): 012409, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32794969

RESUMEN

Recent advances in next generation sequencing-based single-cell technologies have allowed high-throughput quantitative detection of cell-surface proteins along with the transcriptome in individual cells, extending our understanding of the heterogeneity of cell populations in diverse tissues that are in different diseased states or under different experimental conditions. Count data of surface proteins from the cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) technology pose new computational challenges, and there is currently a dearth of rigorous mathematical tools for analyzing the data. This work utilizes concepts and ideas from Riemannian geometry to remove batch effects between samples and develops a statistical framework for distinguishing positive signals from background noise. The strengths of these approaches are demonstrated on two independent CITE-seq data sets in mouse and human.


Asunto(s)
Proteínas de la Membrana/metabolismo , Modelos Biológicos , Análisis de la Célula Individual , Animales , Reacciones Falso Positivas , Perfilación de la Expresión Génica , Humanos , Proteínas de la Membrana/genética , Ratones
13.
iScience ; 23(10): 101582, 2020 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-33205009

RESUMEN

Inflammatory response heterogeneity has impeded high-resolution dissection of diverse immune cell populations during activation. We characterize mouse cutaneous immune cells by single-cell RNA sequencing, after inducing inflammation using imiquimod and oxazolone dermatitis models. We identify 13 CD45+ subpopulations, which broadly represent most functionally characterized immune cell types. Oxazolone pervasively upregulates Jak2/Stat3 expression across T cells and antigen-presenting cells (APCs). Oxazolone also induces Il4/Il13 expression in newly infiltrating basophils, and Il4ra and Ccl24, most prominently in APCs. In contrast, imiquimod broadly upregulates Il17/Il22 and Ccl4/Ccl5. A comparative analysis of single-cell inflammatory transcriptional responses reveals that APC response to oxazolone is tightly restricted by cell identity, whereas imiquimod enforces shared programs on multiple APC populations in parallel. These global molecular patterns not only contrast immune responses on a systems level but also suggest that the mechanisms of new sources of inflammation can eventually be deduced by comparison to known signatures.

14.
Sci Rep ; 9(1): 10335, 2019 07 17.
Artículo en Inglés | MEDLINE | ID: mdl-31316132

RESUMEN

Multiple lines of evidence have shown that systemic lupus erythematosus (SLE) is attributable to both genetic and environmental factors. The product of GRB2 is a key factor in the activation of B cells and has been reported to be significantly associated with SLE in European populations. In the study, we aimed to investigate the relationship between GRB2 and SLE. A total of 1,710 Han Chinese women comprising 567 SLE patients and 1,143 controls were recruited to genotype 20 selected tagging SNPs. We tested the potential association between 13 clinical variables of SLE and the significant polymorphisms related to SLE. The eQTL data were extracted from the GTEx database to examine the functional consequences of the targeted SNPs. A significant association signal was identified between rs36023980 and SLE in both genotypic and allelic analyses (OR = 0.61, P = 0.0003). Complement inhibition was shown to be significantly associated with the genotypes of SNP rs36023980 in SLE patients (Pgenotype = 0.003). Further stratification analyses showed that the genetic association signal of SNP rs36023980 on SLE could only be identified in cases with complement inhibition. SNP rs36023980 was also identified to be significantly associated with the expression of GRB2 in whole blood and sun-exposed skin. In conclusion, our findings confirm the results from the previous GWAS and are the first to report the association of GRB2 with SLE in Han Chinese population.


Asunto(s)
Proteína Adaptadora GRB2/genética , Lupus Eritematoso Sistémico/genética , Adulto , Pueblo Asiatico/genética , Estudios de Casos y Controles , China , Proteínas del Sistema Complemento/metabolismo , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Lupus Eritematoso Sistémico/inmunología , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple
15.
J Invest Dermatol ; 139(4): 796-806, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30414907

RESUMEN

Recent studies showed that TWEAK/Fn14 signaling participates in the progression of internal malignancies. However, its role in the biological properties of cutaneous squamous cell carcinoma (SCC) remains unclear. This study was designed to explore the effect of TWEAK/Fn14 activation on cutaneous SCC as well as the relevant mechanism. The expression of TWEAK and Fn14 was determined in tissue samples of patients with cutaneous SCC. Human primary keratinocytes and SCC cell lines were cultured in vitro, receiving stimulation of TWEAK. The xenografts of SCC were generated subcutaneously in BALB/c nude mice. The results showed that both TWEAK and Fn14 were highly expressed in human cutaneous SCC. Moreover, TWEAK/Fn14 activation promoted the proliferation, migration, and invasion of cultured SCC cells. Interestingly, TNFR2 was upregulated in cultured SCC cells, and the transfection of TNFR2 small interfering RNA abrogated the effect of TWEAK on these cells. Finally, the favorable effect of TWEAK/Fn14 signals was confirmed in BALB/c nude mice with SCC xenografts. In conclusion, TWEAK/Fn14 signals contribute to the progression of cutaneous SCC, possibly involving the TNF-α-independent TNFR2 signal transduction.


Asunto(s)
Carcinoma de Células Escamosas/genética , ADN de Neoplasias/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Cutáneas/genética , Piel/patología , Receptor de TWEAK/genética , Western Blotting , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Proliferación Celular , Progresión de la Enfermedad , Humanos , Inmunohistoquímica , Transducción de Señal , Piel/metabolismo , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/patología , Receptor de TWEAK/biosíntesis
16.
J Invest Dermatol ; 139(1): 224-234, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30081003

RESUMEN

TWEAK acts by engaging with Fn14 to regulate inflammatory responses, fibrosis, and tissue remodeling, which are central in the repair processes of wounds. This study aims to explore the potential role of the TWEAK/Fn14 pathway in the healing of cutaneous burn wounds. Third-degree burns were introduced in wild-type and Fn14-deficient BALB/c mice, followed by evaluation of wound areas and histological changes. The downstream cytokines including growth factors were also examined in lesional skin. Moreover, human dermal microvascular endothelial cells and dermal fibroblasts were analyzed in vitro upon TWEAK stimulation. The healing of burn wounds was delayed in Fn14-deficient mice and was accompanied by the suppression of inflammatory responses, growth factor production, and extracellular matrix synthesis. Moreover, TWEAK/Fn14 activation enhanced the migration and cytokine production of both dermal microvascular endothelial cells and dermal fibroblasts. TWEAK also facilitates the expression of α-SMA and palladin in dermal fibroblasts. Furthermore, transfection of Fn14 small interfering RNA abrogated such promotion effect of TWEAK on these cells. In conclusion, TWEAK/Fn14 signals mediate the healing of burn wounds, possibly involving TWEAK regulation of the function of resident cells.


Asunto(s)
Quemaduras/genética , Regulación de la Expresión Génica , ARN/genética , Piel/patología , Receptor de TWEAK/genética , Cicatrización de Heridas/genética , Animales , Quemaduras/metabolismo , Quemaduras/patología , Células Cultivadas , Modelos Animales de Enfermedad , Ratones Endogámicos BALB C , Ratones Noqueados , Reacción en Cadena de la Polimerasa , Transducción de Señal , Piel/metabolismo , Receptor de TWEAK/biosíntesis
17.
Front Pharmacol ; 9: 660, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29977207

RESUMEN

The interaction of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor fibroblast growth factor inducible 14 (Fn14) participates in inflammatory responses, fibrosis, and tissue remodeling, which are central in the repair processes of wounds. Fn14 is expressed in main skin cells including dermal fibroblasts. This study was designed to explore the therapeutic effect of TWEAK on experimental burn wounds and the relevant mechanism underlying such function. Third-degree burns were introduced in two BALB/c mouse strains. Recombinant TWEAK was administrated topically, followed by the evaluation of wound areas and histologic changes. Accordingly, the downstream cytokines, inflammatory cell infiltration, and extracellular matrix synthesis were examined in lesional tissue. Moreover, the differentiation markers were analyzed in cultured human dermal fibroblasts upon TWEAK stimulation. The results showed that topical TWEAK accelerated the healing of burn wounds in wild-type mice but not in Fn14-deficient mice. TWEAK strengthened inflammatory cell infiltration, and exaggerated the production of growth factor and extracellular matrix components in wound areas of wild-type mice. Moreover, TWEAK/Fn14 activation elevated the expression of myofibroblastic differentiation markers, including alpha-smooth muscle actin and palladin, in cultured dermal fibroblasts. Therefore, topical TWEAK exhibits therapeutic effect on experimental burn wounds through favoring regional inflammation, cytokine production, and extracellular matrix synthesis. TWEAK/Fn14 activation induces the myofibroblastic differentiation of dermal fibroblasts, partially contributing to the healing of burn wounds.

18.
Sci Rep ; 8(1): 13001, 2018 08 29.
Artículo en Inglés | MEDLINE | ID: mdl-30158536

RESUMEN

Vitiligo is a skin disease that affects 1% of the population worldwide. Both environmental and genetic factors contribute to the risk of vitiligo. GZMB encodes the enzyme Granzyme B, which plays an important role in cytotoxic T cell-induced apoptosis, and it has been considered one of the candidate genes for vitiligo because of its connections with human immune system. Overall, 3,120 study subjects with Chinese Han ancestry were recruited, and 15 pre-selected SNPs of GZMB were genotyped. Genetic association analyses were performed to evaluate the genetic risk of these SNPs to vitiligo. Further bioinformatic analyses were conducted to examine the potential biological function of targeted SNPs. The SNP rs8192917, a non-synonymous coding SNP, was identified to be significantly associated with the disease status of vitiligo, with OR = 1.39 and P = 1.92 × 10-8. Differences in the association signal can be observed in the stratification analyses of multiple clinical variables. Our positive results provide additional supportive evidence that GZMB gene is an important locus for vitiligo in Han Chinese population.


Asunto(s)
Granzimas/genética , Polimorfismo de Nucleótido Simple , Vitíligo/genética , Adulto , Pueblo Asiatico , Femenino , Estudios de Asociación Genética , Genotipo , Humanos , Masculino , Adulto Joven
19.
Front Immunol ; 8: 1752, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29276517

RESUMEN

Bullous pemphigoid (BP) is by far the most common autoimmune blistering dermatosis that mainly occurs in the elderly. The BP180 is a transmembrane glycoprotein, which is highly immunodominant in BP. The structure and location of BP180 indicate that it is a significant autoantigen and plays a key role in blister formation. Autoantibodies from BP patients react with BP180, which leads to its degradation and this has been regarded as the central event in BP pathogenesis. The consequent blister formation involves the activation of complement-dependent or -independent signals, as well as inflammatory pathways induced by BP180/anti-BP180 autoantibody interaction. As a multi-epitope molecule, BP180 can cause dermal-epidermal separation via combining each epitope with specific immunoglobulin, which also facilitates blister formation. In addition, some inflammatory factors can directly deplete BP180, thereby leading to fragility of the dermal-epidermal junction and blister formation. This review summarizes recent investigations on the role of BP180 in BP pathogenesis to determine the potential targets for the treatment of patients with BP.

20.
Front Immunol ; 8: 651, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28620393

RESUMEN

Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) binds to its sole receptor fibroblast growth factor-inducible 14 (Fn14), participating in various inflammatory responses. Recently, TWEAK/Fn14 activation was found prominent in the lesions of cutaneous lupus erythematosus (CLE). This study was designed to further reveal the potential role of this pathway in Ro52-mediated photosensitization. TWEAK, Fn14, and Ro52 were determined in the skin lesions of patients with CLE. Murine keratinocytes received ultraviolet B (UVB) irradiation or plus TWEAK stimulation and underwent detection for Ro52 and proinflammatory cytokines. The chemotaxis of J774.2 macrophages was evaluated on TWEAK stimulation of cocultured keratinocytes. We found that TWEAK, Fn14, and downstream cytokines were highly expressed in CLE lesions that overexpressed Ro52. Moreover, TWEAK enhanced the UVB-induced Ro52 upregulation in murine keratinocytes. Meanwhile, TWEAK stimulation of keratinocytes favored the migration of macrophages through promoting the production of chemokine C-C motif ligands 17 and 22. Furthermore, Fn14 siRNA transfection or nuclear factor-kappa B (NF-κB) inhibitor abrogated the TWEAK enhancement of Ro52 expression in keratinocytes. Similarly, TNF receptor associated factor 2 (TRAF2) siRNA reduced the protein level of Ro52 in these cells upon TWEAK stimulation. Interestingly, UVB irradiation increased the expression of TNF receptor type 1 (TNFR1) but not affecting TNFR2 expression in keratinocytes. In conclusion, the TWEAK/Fn14 signaling participates in Ro52-mediated photosensitization and involves the activation of NF-κB pathway as well as the function of the TRAF2/TNFR partners.

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