Wu Wei, Xie Feng, Zhang Yi, Wang Xiuxia, Xia Lingling, Wu Xiaoli, Gao Zhen
Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China.
Biomedcial Research Center, Shanghai Zhong Shan Hospital, Fudan University Shanghai, China.
Int J Clin Exp Pathol. 2018 Apr 1;11(4):1866-1877. eCollection 2018.
Fibronectin (FN) plays a critical role in the development and progression of keloid scarring (KS). In the present study, we hypothesized that a post-translational mechanism of microRNAs regulated the expression of FN in keloid scarring fibroblasts (KSFBs). Here, we collected 20 KS tissues and paired corresponding adjacent normal tissues from clinical patients and measured the expression of miRNA-217. First, by using PicTar, TargetScan and miRBase database, we found that miRNA-217 might be a regulator of FN in human species. Based on these hypotheses, the expression of miRNA-217 and FN in KS tissues was investigated. The results demonstrated that the expression of miRNA-217 was greatly suppressed, and FN was increased in KS tissues. Intriguingly, the expression levels of endogenous miRNA-217 negatively correlated with the FN mRNA levels (Pearson's correlation coefficient = -0.683, < 0.001). In vitro, miRNA-217 could regulate FN through the predicted binding sites in its 3'-UTR. miRNA-217 played an impact on cell proliferation and apoptosis, thereby regulating KSFBs growth. Moreover, miRNA-217 gain-of function decreased FN, Col-1 and Col-3 protein expression, and miRNA-217 loss-of function increased FN, Col-1 and Col-3 protein expression in KSFBs. In conclusion, overexpressed miRNA-217 could inhibit KSFBs growth, and the underlying mechanism was mediated, at least partially, through the suppression of FN expression. But above all, miRNA-217 might play a potential therapeutic avenue for the treatment of keloid fibrogenesis.
纤连蛋白（FN）在瘢痕疙瘩（KS）的发生和发展中起关键作用。在本研究中，我们假设微小RNA的一种翻译后机制调节瘢痕疙瘩成纤维细胞（KSFBs）中FN的表达。在此，我们收集了20例临床患者的KS组织及配对的相应相邻正常组织，并检测了miRNA - 217的表达。首先，通过使用PicTar、TargetScan和miRBase数据库，我们发现miRNA - 217可能是人类FN的调节因子。基于这些假设，研究了KS组织中miRNA - 217和FN 的表达。结果表明，KS组织中miRNA - 217的表达受到极大抑制，而FN增加。有趣的是，内源性miRNA - 217的表达水平与FN mRNA水平呈负相关（Pearson相关系数= - 0.683，<0.001）。在体外，miRNA - 217可通过其3'-UTR中的预测结合位点调节FN。miRNA - 217对细胞增殖和凋亡有影响，从而调节KSFBs的生长。此外，miRNA - 217功能获得性降低了KSFBs中FN、Col - 1和Col - 3蛋白的表达，而miRNA - 217功能缺失性增加了KSFBs中FN、Col - 1和Col - 3蛋白的表达。总之，过表达的miRNA - 217可抑制KSFBs的生长，其潜在机制至少部分是通过抑制FN的表达介导的。但最重要的是，miRNA - 217可能为瘢痕疙瘩纤维化的治疗提供一条潜在的治疗途径。
