title: MiR-1908 promotes scar formation post-burn wound healing by suppressing Ski-mediated inflammation and fibroblast proliferation.
abstract: 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.
authors.affiliation: Department of Burns Surgery, The First Hospital of Jilin University, No.71, Xinmin Street, Changchun, 130021, China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Xie
authors.affiliation: Department of Burns Surgery, The First Hospital of Jilin University, No.71, Xinmin Street, Changchun, 130021, China. beginkaishi@163.com.
authors.forename: Kai
authors.initials: K
authors.lastname: Shi
authors.affiliation: Department of Burns Surgery, The First Hospital of Jilin University, No.71, Xinmin Street, Changchun, 130021, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Burns Surgery, The First Hospital of Jilin University, No.71, Xinmin Street, Changchun, 130021, China.
authors.forename: Jingchun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Burns Surgery, The First Hospital of Jilin University, No.71, Xinmin Street, Changchun, 130021, China.
authors.forename: Jiaao
authors.initials: J
authors.lastname: Yu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001483:Base Sequence; D002056:Burns / Q000150:complications / Q000235:genetics / Q000473:pathology*; D049109:Cell Proliferation; D002921:Cicatrix / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020405:Dermis / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D005355:Fibrosis; D020868:Gene Silencing; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000473:pathology*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics; D014945:Wound Healing / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; C577645:MIRN1908 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C060614:SKI protein, human
keywords: Burn wound; Fibroblast proliferation; Scar formation; Ski; miR-1908