A5100668997- Systemic Sclerosis and Related Diseases
- Wnt/β-catenin signaling in development and cancer
- Skin and Cellular Biology Research
- Dermatologic Treatments and Research
- Connective Tissue Growth Factor Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Fibroblast Growth Factor Research
- Kruppel-like factors research
- Dermatological and Skeletal Disorders
- Sirtuins and Resveratrol in Medicine
- Inflammatory Myopathies and Dermatomyositis
- Trigeminal Neuralgia and Treatments
- Calcium signaling and nucleotide metabolism
- Hepatitis B Virus Studies
- Hepatitis C virus research
- Polyomavirus and related diseases
- Head and Neck Anomalies
- Hops Chemistry and Applications
- Teratomas and Epidermoid Cysts
- Nosocomial Infections in ICU
- Genomics, phytochemicals, and oxidative stress
- Skin Diseases and Diabetes
- Tuberculosis Research and Epidemiology
- HIV, TB, and STIs Epidemiology
- Cerebral Venous Sinus Thrombosis
Northwestern University
2020
Northwestern University
2009-2020
First Affiliated Hospital of Gannan Medical University
2013-2019
Gannan Medical University
2019
Nanjing University of Chinese Medicine
2019
Peking University
2017
Scleroderma Foundation
2017
Peking University People's Hospital
2017
Capital Medical University
2014
Dalian Medical University
2014
Objective Accumulation of myofibroblasts in fibrotic skin is a hallmark systemic sclerosis (SSc; scleroderma), but the origins these cells remain unknown. Because loss intradermal adipose tissue consistent feature cutaneous fibrosis, we sought to examine hypothesis that populating dermis derive from adipocytic progenitors. Methods We performed genetic fate mapping studies investigate and its potential role fibrosis mice with bleomycin‐induced scleroderma. Modulation phenotypes ex vivo was...
Objective.Because aberrant Wnt signaling has been linked with systemic sclerosis (SSc) and pulmonary fibrosis, we sought to investigate the effect of Wnt-10b on skin homeostasis differentiation in transgenic mice explanted mesenchymal cells.Methods.The expression patients SSc a mouse model fibrosis was investigated.The phenotype biochemical characteristics Wnt-10b-transgenic were evaluated.The vitro effects ectopic examined fibroblasts preadipocytes.Results.The increased lesional biopsy...
The nuclear orphan receptor peroxisome proliferator-activated receptor-gamma (PPAR-γ) is expressed in multiple cell types addition to adipocytes. Upon its activation by natural ligands such as fatty acids and eicosanoids, or synthetic agonists rosiglitazone, PPAR-γ regulates adipogenesis, glucose uptake inflammatory responses. Recent studies establish a novel role for signaling an endogenous mechanism regulating transforming growth factor-ß (TGF-ß)-dependent fibrogenesis. Here, we sought...
// Kaname Akamata 1,* , Jun Wei Mitra Bhattacharyya 1 Paul Cheresh 2 Michael Y. Bonner 3 Jack L. Arbiser 3,4 Kirtee Raparia 5 Mahesh P. Gupta 6 David W. Kamp 2,7 and John Varga Division of Rheumatology, Feinberg School Medicine, Northwestern University, Chicago, IL, USA Pulmonary & Critical Care Department Dermatology, Emory University Atlanta, GA, 4 Atlanta Veterans Administration Medical Center Winship Cancer, Pathology, Surgery, 7 Jesse Brown VA Center, * These authors have...
Rationale: Fibrosis leads to failure of the skin, lungs, and other organs in systemic sclerosis; accounts for substantial morbidity mortality; lacks effective therapy. Myofibroblast activation underlies organ fibrosis, but key extracellular cues driving persistence process remain incompletely characterized. Objectives: The objectives were evaluate IL6/JAK/STAT axis associated with fibrosis skin lung biopsies from sclerosis patients effects Food Drug Administration–approved JAK/STAT...
Abstract Introduction Fibrosis in scleroderma is associated with collagen deposition and myofibroblast accumulation. Peroxisome proliferator activated receptor gamma (PPAR-γ), a master regulator of adipogenesis, inhibits profibrotic responses induced by transforming growth factor-ß (TGF-β), its expression impaired scleroderma. The roles adiponectin, PPAR-γ regulated pleiotropic adipokine, regulating the response fibroblasts mediating effects are unknown. Methods Regulation fibrotic gene...
Abstract Introduction Progressive fibrosis in systemic sclerosis (SSc) is linked to aberrant transforming growth factor beta (TGF-beta) signaling. Peroxisome proliferator-activated receptor gamma (PPAR-gamma) blocks fibrogenic TGF-beta responses vitro and vivo . Reduced expression function of PPAR-gamma patients with SSc may contribute progression fibrosis. Here we evaluated the levels adiponectin, a sensitive specific index activity, as potential biomarker SSc. Methods Adiponectin were...
Persistent fibroblast activation underlies skin fibrosis in systemic sclerosis (SSc), but the transcriptional and epigenetic mechanisms controlling this process are not well understood. In view of potent influence acetylation status governing tissue fibrosis, we undertook study to investigate expression antiaging deacetylase enzyme sirtuin 1 (SIRT1) SSc its effects on fibrotic responses vitro vivo. Tissue SIRTs was interrogated from publicly available genome-wide data sets by...
Skin fibrosis in systemic sclerosis (SSc) is accompanied by attrition of dermal white adipose tissue (dWAT) and reduced levels circulating adiponectin. Since adiponectin has potent regulatory effects on fibroblasts, we sought to assess signaling SSc skin biopsies, evaluate mice with gain- loss-of-function mutations. Furthermore, investigated the mechanism action agonist peptides targeting receptors vitro vivo. We found that pathway activity was significantly a subset biopsies. Mice lacking...
<h3>Background</h3> Persistent fibroblast activation initiated by transforming growth factor β (TGF-β) is a fundamental event in the pathogenesis of systemic sclerosis, and its pharmacological inhibition represents potential therapeutic strategy. The nuclear receptor, peroxisome proliferator-activated receptor γ (PPAR-γ), exerts potent fibrotic activity. synthetic oleanane triterpenoid, 2-cyano-3,12-dioxo-olean-1,9-dien-28-oic acid (CDDO), PPAR-γ agonist with effects on TGF-β signalling...
Members of the early growth response (Egr) gene family transcription factors have nonredundant biological functions. Although Egr-3 is implicated primarily in neuromuscular development and immunity, its regulation role tissue repair fibrosis has not been studied. We now show that normal skin fibroblasts, was potently induced by transforming factor-β via canonical Smad3. Moreover, transient overexpression sufficient to stimulate fibrotic expression, whereas deletion resulted substantially...
Although transforming growth factor β (TGFβ) is recognized as being a key trigger of fibroblast activation in systemic sclerosis (SSc), prominent innate immunity suggests that additional pathways contribute to disease persistence. Toll-like receptor 9 (TLR9) implicated autoimmunity and fibrosis; however, the expression, mechanism action, pathogenic role TLR9 signaling SSc remain uncharacterized. The aim this study was explore activity, potential context skin fibrosis mouse models...
The processes underlying synchronous multiple organ fibrosis in systemic sclerosis (SSc) remain poorly understood. Age-related pathologies are associated with organismal decline nicotinamide adenine dinucleotide (NAD+) that is due to dysregulation of NAD+ homeostasis and involves the NADase CD38. We now show CD38 upregulated patients diffuse cutaneous SSc, levels skin associate molecular signatures, as well clinical scores, while expression key NAD+-synthesizing enzymes unaltered. Boosting...
Objective Understanding the pathogenesis of systemic sclerosis (SSc) is confounded by considerable disease heterogeneity. Animal models SSc that recapitulate distinct subsets at molecular level have not been delineated. We applied interspecies comparative analysis genomic data from multiple mouse and patients with to determine which animal best reflect intrinsic subsets. Methods Gene expression measured in skin mice sclerodermatous graft‐versus‐host (GVHD), bleomycin‐induced fibrosis, Tsk1/+...
The eis gene of Mycobacterium tuberculosis has been shown to play a role in the survival avirulent smegmatis within macrophage. In vitro and vivo analysis Deltaeis deletion mutants complemented strains showed no effect on M. U-937 macrophages or mouse aerosol infection model, respectively. Further studies were done an attempt determine intracellular define phenotypic difference between wild-type mutant. Bioinformatic indicated that Eis is acetyltransferase GCN5-related family...
Fibrosis in systemic sclerosis (SSc), a complex polygenic disease associated with autoimmunity and proliferative/obliterative vasculopathy, shares pathobiologic features common other fibrosing illnesses, but also has distinguishing characteristics. Fibroblast activation induced by transforming growth factor-β (TGF-β), Wnts innate immune receptors, along oxidative stress reactive oxygen species (ROS) are implicated pathogenesis. On the hand, roles of endothelial-mesenchymal differentiation...
A cross-sectional survey was conducted to determine seroprevalence and correlates of coinfections hepatitis B virus (HBV), C (HCV), Epstein-Bar (EBV), herpes simplex including type 1 (HSV-1) 2 (HSV-2) among human immunodeficiency (HIV)/acquired syndrome (AIDS) patients in China. total 1,110 HIV/AIDS from Shanxi (Central area, n = 287), Zhejiang (Eastern 163), Yunnan (Southwestern 300) Xinjiang (Northwestern 360) provinces were analyzed. The overall 6.3% for HBsAg, 59.0% anti-HCV IgG, 96.6%...
By stimulating collagen synthesis and myofibroblasts differentiation, transforming growth factor-β (TGF- β) plays a pivotal role in tissue repair fibrosis. The early response-1 (Egr-1) transcription factor mediates profibrotic TGF-β responses, its expression is elevated biopsies from patients with scleroderma. NGF1-A-binding protein 2 (Nab2) conserved transcriptional cofactor that directly binds to Egr-1 positively or negatively modulates target gene transcription. Despite the recognized...
Abstract Irritable bowel syndrome (IBS) is a common disorder of unknown etiology. Studies have found close relation between IBS and microRNAs (miRNAs), but the study concerning relationship miR‐181c‐5p in still blank. Thus, this aims to explore role via interleukin 1α (IL1A). Initially, microarray analysis was used retrieve genes related predict miRNAs regulating IL1A gene. model then established with abdominal withdraw reflection (AWR) Bristol stool grading mice measured. Afterwards,...