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Rosiglitazone alleviates the persistent fibrotic phenotype of lesional skin scleroderma fibroblasts. 2010

Xu Shi-wen, and Mark Eastwood, and Richard J Stratton, and Christopher P Denton, and Andrew Leask, and David J Abraham
Centre for Rheumatology, University College London (Royal Free Campus), London, UK.

OBJECTIVE The transcription factor peroxisome proliferator-activated receptor (PPAR)-gamma plays an important role in controlling cell differentiation. The aim of the present study was to examine whether PPAR-gamma expression was reduced in skin scleroderma fibroblasts and whether PPAR-gamma agonists could suppress the persistent fibrotic phenotype of skin scleroderma fibroblasts. METHODS Dermal fibroblasts were isolated from site-, age- and sex-matched healthy individuals and lesional areas of individuals with dcSSc. Western blot and collagen gel contraction analyses were used to detect protein expression in the presence or absence of the PPAR-gamma agonist rosiglitazone. RESULTS PPAR-gamma expression was reduced in dcSSc fibroblasts. The PPAR-gamma agonist rosiglitazone alleviated the persistent fibrotic phenotype of dcSSc fibroblasts. CONCLUSIONS Rosiglitazone may alleviate the extent of fibrosis in dcSSc.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D010641 Phenotype The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment. Phenotypes
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D005260 Female Females
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast
D005355 Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Cirrhosis,Fibroses
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077154 Rosiglitazone A thiazolidinedione that functions as a selective agonist for PPAR GAMMA. It improves INSULIN SENSITIVITY in adipose tissue, skeletal muscle, and the liver of patients with TYPE 2 DIABETES MELLITUS. 5-((4-(2-Methyl-2-(pyridinylamino)ethoxy)phenyl)methyl)-2,4-thiazolidinedione-2-butenedioate,Avandia,BRL 49653,BRL-49653,BRL49653,Rosiglitazone Maleate
D000199 Actins Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle. F-Actin,G-Actin,Actin,Isoactin,N-Actin,alpha-Actin,alpha-Isoactin,beta-Actin,gamma-Actin,F Actin,G Actin,N Actin,alpha Actin,alpha Isoactin,beta Actin,gamma Actin

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