MicroRNA‑185 regulates transforming growth factor‑β1 and collagen‑1 in hypertrophic scar fibroblasts.
MicroRNA‑185 regulates transforming growth factor‑β1 and collagen‑1 in hypertrophic scar fibroblasts.
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DOI：
10.3892/mmr.2017.6179
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发表时间：
2017-04
影响因子：
3.4
通讯作者：
Gao Z
中科院分区：
文献类型：
--
作者：
Xiao K;Luo X;Wang X;Gao Z
转化生长因子-β-1和I型胶原在增生性瘢痕的发生发展中起重要作用。本研究假设，在HS成纤维细胞中，MicroRNAs的翻译后机制调节转化生长因子-β-1和COL-1的表达。收集20例HS组织，与临床上相应的正常组织进行比较，检测miR-185的表达。利用PicTar、TargetScan和miRbase数据库，可以确定miR-185可能是人类转化生长因子-β-1和COL-1的调节因子。基于这些假设，我们研究了miR185、转化生长因子β1和COL-1在HS组织中的表达。结果表明，在HS组织中，miR185的表达明显受到抑制，而转化生长因子β1和COL 1的水平明显升高。内源性miR185表达水平与转化生长因子β1、COL 1mRNA表达水平呈负相关(皮尔逊相关系数r=−0.674，P<0.0 1；r=−0.590，P<0.01)。在体外，miR185可以通过其3‘-非翻译区的预测结合位点来调节转化生长因子-β-1和COL-1。MIR-185对细胞增殖和凋亡有影响，从而调节HSFB的生长。此外，miR-185功能获得降低转化生长因子-β1和COL-1蛋白表达，而miR-185功能丧失增加转化生长因子-β1和COL-1蛋白表达。结论：过表达miR-185可以抑制HSFB的生长，其机制至少部分是通过抑制转化生长因子-β-1和COL-1的表达来实现的。然而，最重要的是，miR-185可能成为治疗HS的一种潜在的治疗方法。
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.