miRNA-150-5p promotes hepatic stellate cell proliferation and sensitizes hepatocyte apoptosis during liver fibrosis
miRNA-150-5p promotes hepatic stellate cell proliferation and sensitizes hepatocyte apoptosis during liver fibrosis
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肝纤维化过程中miRNA-150-5p促进肝星状细胞增殖并敏感肝细胞凋亡
DOI：
10.2217/epi-2019-0104
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发表时间：
2020-01-01
期刊：
影响因子：
3.8
通讯作者：
You, Hong
中科院分区：
文献类型：
--
作者：
Chen, Wei;Yan, Xuzhen;You, Hong
目的：探讨miRNA-150- 5 p（miR-150- 5 p）在肝纤维化中的作用。材料和方法：采用miRNA表达谱、CCl 4诱导的肝纤维化进展和消退啮齿动物模型、定量实时PCR、miR-150- 5 p模拟物和抑制剂、细胞增殖和凋亡检测、RNA测序和生物信息学分析。结果如下：miR-150- 5 p的表达与肝纤维化的进展和消退呈正相关，但miR-150- 5 p的表达具有细胞特异性，即在肝纤维化过程中，miR-150- 5 p在肝星状细胞（hepatic stellate cells，HSC）中表达增强，而在HSC中表达减少，miR-150- 5 p过表达促进HSC凋亡，致敏肝细胞凋亡; miR-150- 5 p模拟物对HSC转录组稳定性的影响大于肝细胞; miR-150- 5 p介导的干扰素信号通路激活可能是HSC凋亡的原因。结论：miR-150- 5 p在肝纤维化过程中对HSC和肝细胞的调控和作用模式相反。
Aim: To explore the role of miRNA-150-5p (miR-150-5p) in liver fibrosis. Materials & methods: miRNA expression profiles, CCl4-induced liver fibrosis progression and regression rodent models, quantitative realtime PCR, miR-150-5p mimics and inhibitors, cell proliferation and apoptosis detection, RNA sequencing and bioinformatics analysis were employed. Results: Liver tissuemiR-150-5p expression was positively associated with liver fibrosis progression and regression; however, miR-150-5p exhibited a cell-specific expression pattern, namely, it was enhanced in hepatocytes but reduced in hepatic stellate cells (HSCs) during liver fibrosis; miR-150-5p overexpression promoted HSC apoptosis and sensitized hepatocyte apoptosis; miR-150-5p mimic had a larger influence on the transcriptomic stability of HSCs than that of hepatocytes; miR-150-5p mediated activation of interferon signaling pathways might be responsible for HSC apoptosis. Conclusion: miR-150-5p exhibited an opposite regulation and function pattern between HSCs and hepatocytes during liver fibrosis.