Fibroproliferative effect of microRNA-21 in hypertrophic scar derived fibroblasts

Hypertrophic scar (HS) is a fibroproliferative disorder caused by abnormal wound healing, which is characterized by excessive deposition of extracellular matrix (ECM) secreted by fibroblasts. We previous have found that expression of microRNA-21(miR-21) was increased in tissues and fibroblasts of HS. However, the underlying molecular mechanism remains to be further elucidated. In this study, we identified the miR-21 was a marker for the phenotype of HS fibroblasts, as anti-miR-21 reduced expression of fibrosis markers such as Col1A1, Col3A1, Fn and alpha-SMA in fibroblasts and overexpression of miR-21 promoted fibroproliferative expression in fibroblasts. Furthermore, we also found that miR-21 promoted TGF-beta 1 induced fibroproliferative expression by repressing Smad7 expression in vitro. In addition, the miR-21 inhibitor inhibited the growth of hypertrophic scar tissue in vivo (nude mice experimental model). These results indicated that miR-21 was a critical regulator for HS formation and TGF-beta 1/rniR-21/Smad7 pathway could be a useful therapeutic target for the treatment of HS. (C) 2016 Elsevier Inc. All rights reserved.