Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist inhibits collagen synthesis in human hypertrophic scar fibroblasts by targeting Smad3 via miR-145

摘要

The transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-gamma) functions to regulate cell differentiation and lipid metabolism. Recently, its agonist has been documented to regulate extracellular matrix production in human dermal fibroblasts. This study explored the underlying molecular mechanisms and gene interactions in hypertrophic scar fibroblasts (HSFBs) in vitro. FISFBs were cultured and treated with or without PPAR-gamma agonist or antagonist for gene expression. Bioinformatical analysis predicted that miR-145 could target Smad3 expression. Luciferase assay was used to confirm such an interaction. The data showed that PPAR-y agonist troglitazone suppressed expression of Smad3 and Coll in HSFBs. PPAR-gamma agonist induced miR-145 at the gene transcriptional level, which in turn inhibited Smad3 expression and Coll level in HSFBs. Furthermore, ELISA data showed that Coll level in HSFBs was controlled by a feedback regulation mechanism involved in PPAR-gamma agonist and antagonist-regulated expression of miR-145 and Smad3 in HSFBs. These findings indicate that PPAR-gamma-miR-145-Smad3 axis plays a role in regulation of collagen synthesis in HSFBs. (C) 2015 Elsevier Inc. All rights reserved.