MicroRNA-192 regulates hypertrophic scar fibrosis by targeting SIP1

• Published in: Journal of molecular histology Vol. 48; no. 5-6; pp. 357 - 366
• Main Authors: Li, Yan, Zhang, Julei, Zhang, Wei, Liu, Yang, Li, Yuehua, Wang, Kejia, Zhang, Yijie, Yang, Chen, Li, Xiaoqiang, Shi, Jihong, Su, Linlin, Hu, Dahai
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.12.2017; Springer Nature B.V
• Subjects: Actins - metabolism; Adult; Animals; Base Sequence; Binding Sites; Biomedical and Life Sciences; Biomedicine; Bleomycin; Cell Biology; Cicatrix, Hypertrophic - genetics; Cicatrix, Hypertrophic - pathology; Collagen; Collagen - biosynthesis; Developmental Biology; Disease Models, Animal; Fibroblasts; Fibroblasts - metabolism; Fibroblasts - pathology; Fibrosis; Gene Expression Regulation; Gene Knockdown Techniques; Humans; Kidneys; Life Sciences; Male; Mice, Inbred BALB C; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Myofibroblasts - metabolism; Myofibroblasts - pathology; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Original Paper; Protein Binding; RNA, Small Interfering - metabolism; RNA-Binding Proteins - genetics; RNA-Binding Proteins - metabolism; Rodents; siRNA; Skin; Smad protein; Zinc Finger E-box Binding Homeobox 2 - metabolism; SIP1; Myofibroblasts; Hypertrophic scars; MiR-192; Collagen
• ISSN: 1567-2379; 1567-2387
• DOI: 10.1007/s10735-017-9734-3

Hypertrophic scar (HS) is a fibro-proliferative disorder which is characterized by excessive deposition of collagen and accumulative activity of myofibroblasts. Increasing evidences have demonstrated miRNAs play a pivotal role in the pathogenesis of HS. MiR-192 is closely associated with renal fibrosis, but its effect on HS formation and skin fibrosis remains unknown. In the study, we presented that miR-192 was up-regulated in HS and HS derived fibroblasts (HSFs) compared to normal skin (NS) and NS derived fibroblasts (NSFs), accompanied by the reduction of smad interacting protein 1 (SIP1) expression and the increase of Col1, Col3 and α-SMA levels. Furthermore, we confirmed SIP1 was a direct target of miR-192 by using luciferase reporter assays. Meanwhile, the overexpression of miR-192 increased the levels of Col1, Col3 and α-SMA. The synthesis of collagen and more positive α-SMA staining were also observed in bleomycin-induced dermal fibrosis model of BALB/c mice treated with subcutaneous miR-192 mimics injection, whereas the inhibition of miR-192 decreased the expression of Col1, Col3 and α-SMA. Moreover, SIP1 siRNA could enhance the levels of Col1, Col3 and α-SMA, showing that the effect of knockdown SIP1 was similar to miR-192 mimics, and the phenomenon manifested miR-192 regulated HS fibrosis by targeting SIP1. Together, our results indicated that miR-192 was a critical factor of HS formation and facilitated skin fibrosis by targeting directly SIP1.