MiR-1908 promotes scar formation post-burn wound healing by suppressing Ski-mediated inflammation and fibroblast proliferation

• DOI: 10.1007/s00441-016-2434-6
• Publication Date: 2016-06-03T01:16:52Z
• Authors: Chunhui Xie; Kai Shi; Xi Zhang; Jingchun Zhao; Jiaao Yu
• Keywords: Inflammation; Male; 0301 basic medicine; Wound Healing; Base Sequence; Dermis; Fibroblasts; Transfection; Fibrosis; Up-Regulation; DNA-Binding Proteins; Cicatrix; MicroRNAs; 03 medical and health sciences; Proto-Oncogene Proteins; Humans; Female; Gene Silencing; RNA, Messenger; Burns; 3' Untranslated Regions; Cell Proliferation

The cell biological basis for scar formation is mainly via excessive fibroblast proliferation accompanied by hypernomic Col I accumulation and inflammation. The role of miR-1908 in scar formation has not been investigated. In this study, we found that miR-1908 expression was inversely associated with the scar suppressor Ski in normal, burn-wounded, healing and scar dermal tissues in humans. Bioinformatics and luciferase reporter gene assays confirmed that miR-1908 targeted the 3'UTR region of Ski mRNA and suppressed Ski expression. Next, human scar epidermal fibroblasts were isolated and the miR-1908 oligonucleotide mimic and inhibitor were respectively transfected into the cells. Western blot analysis proved that Ski expression was sharply reduced by the miR-1908 mimic. MTT and Cell Counting Kit-8 analyses showed that miR-1908 mimic transfection promoted cell proliferation. Simultaneously, data on real-time qPCR analysis indicated that expression of the fibrotic master gene TGF-β1, Ski-suppressing gene Meox2, Col I and proinflammatory markers IL-1α and TNF-α, were all significantly upregulated. In contrast, the miR-1908 inhibitor had a completely opposite effect on cell proliferation and gene expression. The mimic and inhibitor were locally injected into rats with abdominal burn-wounded scars during a 180-day, post-healing experiment. The miR-1908 mimic injection significantly reduced Ski expression, as well as the area, volume and fibrosis of scars in vivo. And, in contrast, the miR-1908 inhibitor injection had an opposite effect to that of the miR-1908 mimic injection. In conclusion, miR-1908 had a positive role in scar formation by suppressing Ski-mediated inflammation and fibroblast proliferation in vitro and in vivo.