MiR-146a-5p suppresses activation and proliferation of hepatic stellate cells in nonalcoholic fibrosing steatohepatitis through directly targeting Wnt1 and Wnt5a

被引：103

作者：

Du, Jinghua ^{[1
]}

Niu, Xuemin ^{[1
]}

Wang, Yang ^{[1
]}

Kong, Lingbo ^{[1
]}

Wang, Rongqi ^{[1
]}

Zhang, Yuguo ^{[1
]}

Zhao, Suxian ^{[1
]}

Nan, Yuemin ^{[1
]}

机构：

[1] Hebei Med Univ, Hosp 3, Dept Tradit & Western Med Hepatol, Shijiazhuang, Peoples R China

来源：

SCIENTIFIC REPORTS | 2015年 / 5卷

关键词：

LIVER FIBROSIS; BETA-CATENIN; MICRORNAS; INFLAMMATION; BIOGENESIS; EXPRESSION; STEATOSIS; INDUCTION; PROGRESS;

D O I：

10.1038/srep16163

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Nonalcoholic fibrosing steatohepatitis is a uniform process throughout nonalcoholic fatty liver disease (NAFLD). MicroRNAs (miRNAs) have been suggested to modulate cellular processes in liver diseases. However, the functional role of miRNAs in nonalcoholic fibrosing steatohepatitis is largely unclear. In this study, we systematically analyzed the hepatic miRNAs by microarray analysis in nonalcoholic fibrosing steatohepatitis in C57BL/6J mice induced by methionine-choline deficient (MCD) diet. We identified 19 up-regulated and 18 down-regulated miRNAs in liver with fibrosis. Among these dysregulated miRNAs, miR-146a-5p was the most significant down-regulated miRNA. Luciferase activity assay confirmed that Wnt1 and Wnt5a were both the target genes of miR-146a-5p. Hepatic miR-146a-5p was down-regulated in fibrosing steatohepatitis, but its target genes Wnt1 and Wnt5a and their consequent effectors alpha-SMA and Col-1 were significantly up-regulated. In addition, miR-146a-5p was downregulated, whilst Wnt1 and Wnt5a were up-regulated in the activated primary hepatic stellate cells (HSCs) compared to the quiescent primary HSCs. Overexpression of miR-146a-5p in HSCs inhibited HSC activation and proliferation, which concomitant with the decreased expressions of Wnt1, Wnt5a, alpha-SMA and Col-1. In conclusion, miR-146a-5p suppresses activation and proliferation of HSCs in the progress of nonalcoholic fibrosing steatohepatitis through targeting Wnt1 and Wnt5a and consequent effectors alpha-SMA and Col-1.

引用

页数：14

共 37 条

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