MicroRNA-185 regulates transforming growth factor-β1 and collagen-1 in hypertrophic scar fibroblasts

Abstract

Transforming growth factor-β1 (TGF-β1) and collagen type I (Col-1) serve a critical role in the development and progression of hypertrophic scarring (HS). The present study hypothesized that a post-translational mechanism of microRNAs (miR) regulated the expression of TGF-β1 and Col-1 in HS fibroblasts (HSFBs). A collection of 20 HS tissues was compared with corresponding normal tissues from clinical patients, and the expression of miR-185 was measured. Using PicTar, TargetScan and miRBase databases, it was identified that miR-185 may be a regulator of TGF-β1 and Col-1 in humans. Based on these hypotheses, the expression of miR-185, TGF-β1 and Col-1 in HS tissues was investigated. The results demonstrated that the expression of miR-185 was markedly suppressed, and TGF-β1 and Col-1 levels were increased, in HS tissues. The expression levels of endogenous miR-185 negatively correlated with the TGF-β1 and Col-1 mRNA levels (Pearson's correlation coefficient r=−0.674, P<0.01 and r=−0.590, P<0.01, respectively). In vitro, miR-185 can regulate TGF-β1 and Col-1 through the predicted binding sites in its 3′-untranslated region. miR-185 had an effect on cell proliferation and apoptosis, thereby regulating HSFBs growth. In addition, miR-185 gain-of-function decreased TGF-β1 and Col-1 protein expression, and miR-185 loss-of-function increased TGF-β1 and Col-1 protein expression in HSFBs. In conclusion, overexpressed miR-185 could inhibit HSFBs growth, and the underlying mechanism was mediated, at least partly, through the suppression of TGF-β1 and Col-1 expression. However, above all, miR-185 might serve as a potential therapeutic approach for the treatment of HS.

Molecular Pathogenesis of Chlamydia Disease Complications: Epithelial-Mesenchymal Transition and Fibrosis

“…In addition, miR-203 targets the EMT-and cell invasion-promoting transcription factor Snail2 (Slug) (34) and SMAD3 (33,34) to prevent fibrosis. Furthermore, among the key downregulated miRNAs, miR-185 targets TGF-␤ and collagen type I to control tissue fibrosis (6,35) and miR-221 targets fibrosis-promoting osteopontin, which is also the target of the polyphenol epigallocatechin-3-gallate (EGCG), which is found in green tea and upregulates miR-221 (36). On the other hand, miR-9 is a key fibrogenic and oncogenic miRNA that targets E-cadherin and the tumor suppressor and transcription SRY-box 7 (SOX7) of the SOX transcription factor family (8,37).…”

miR-93‑mediated collagen expression in stress urinary incontinence via calpain-2

“…Beaumont et al (13) demonstrated that miR-19b expression was reduced in patients with aortic stenosis, which may be a potential biomarker of increased myocardial collagen. Xiao et al (15) observed that in hypertrophic scar fibroblasts, miR-185 regulated the concentration of transforming growth factor-β1 and collagen I. Notably, Jing and Jiang (14) reported that miR-93 regulated collagen loss by targeting stromelysin-1 (MMP3) in human nucleus pulposus cells.…”

Insights into the key roles of epigenetics in matrix macromolecules-associated wound healing

“…Another miRNA downregulated in hypertrophic scars is miR-185. Following bioinformatics target prediction analysis, miR-185 could indeed downregulate expression of TGF-β and collagen I in fibroblasts, affecting cell proliferation and apoptosis [352]. The proteolytic modulation of collagen function is regulated my miRNAs miR-10a and miR-181c, which affect this process in hypertrophic scar fibroblasts by targeting PAI-1 and uPA and increasing MMP-1 levels [353].…”