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miR-185 Inhibits Fibrogenic Activation of Hepatic Stellate Cells and Prevents Liver Fibrosis.
Molecular Therapy - Nucleic Acids ( IF 6.5 ) Pub Date : 2017-11-24 , DOI: 10.1016/j.omtn.2017.11.010
Li Zhou 1 , Shunai Liu 2 , Ming Han 1 , Yanhua Ma 3 , Shenghu Feng 3 , Jing Zhao 3 , Hongping Lu 2 , Xiaoxue Yuan 2 , Jun Cheng 1
Affiliation  

Recent studies have shown the effect of microRNAs on HSC activation and transformation, which is essential for the pathogenesis of liver fibrosis. In our study, we explored the role of miR-185 in liver fibrosis. Plasma miR-185 was detected in hepatitis B virus-related liver fibrosis patients (S2/3, n = 10) by Illumina HiSeq sequencing, and healthy volunteers were selected (n = 8) as the control group. We found that the plasma miR-185 level in fibrosis patients was significantly downregulated. CCl4-induced fibrosis tissues in mouse livers and TGF-β1-activated HSCs also presented downregulated miR-185 concomitant with an increased expression of RHEB and RICTOR. To explore the correlations, LX-2 cells were transiently transfected with miR-185 mimics. The expression levels of α-SMA, collagen I, and collagen III were decreased as well as RHEB and RICTOR. Inhibition of endogenous miR-185 increased fibrogenic activity. Furthermore, dual-luciferase reporter assays indicated that miR-185 inhibited the expression of RHEB and RICTOR by directly targeting their 3′ UTRs. Moreover, silencing RHEB and RICTOR suppressed α-SMA and collagen expression levels. In conclusion, miR-185 prevents liver fibrogenesis by inhibiting HSC activation via inhibition of RHEB and RICTOR. These results provide new insights into the mechanisms behind the anti-fibrotic effect of miR-185.



中文翻译:

miR-185抑制肝星状细胞的纤维化活化并预防肝纤维化。

最近的研究表明,microRNA对HSC激活和转化的影响,这对于肝纤维化的发病机理至关重要。在我们的研究中,我们探索了miR-185在肝纤维化中的作用。通过Illumina HiSeq测序在乙型肝炎病毒相关的肝纤维化患者(S2 / 3,n = 10)中检测到血浆miR-185,并选择健康志愿者(n = 8)作为对照组。我们发现纤维化患者的血浆miR-185水平显着下调。CCl 4诱导的小鼠肝纤维化组织和TGF-β1活化的HSCs也下调了miR-185的表达,并伴随着RHEBRICTOR的表达增加。为了探索相关性,用miR-185模拟物瞬时转染LX-2细胞。α-SMA,胶原I和胶原III的表达水平以及RHEBRICTOR均降低。抑制内源性miR-185可增加纤维化活性。此外,双荧光素酶报告基因检测表明,miR-185通过直接靶向3'UTR来抑制RHEBRICTOR的表达。此外,沉默RHEBRICTOR可抑制α-SMA和胶原蛋白的表达水平。总之,miR-185通过抑制RHEBRICTOR抑制HSC活化来防止肝纤维化。。这些结果为miR-185抗纤维化作用背后的机制提供了新见解。

更新日期:2017-11-24
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