Overexpression miR-125a-5p inhibits HSCs activation and alleviates liver fibrosis through TGF-β/Smad2/3 signaling pathway and autophagy.

IF 7 2区生物学 Q1 CELL BIOLOGY

Cell Death Discovery Pub Date : 2025-09-01 DOI:10.1038/s41420-025-02694-4

Chunyan Zhang, Yabin Zhao, Haoyu Yan, Jianlin Guo, GuoYing Yu

{"title":"Overexpression miR-125a-5p inhibits HSCs activation and alleviates liver fibrosis through TGF-β/Smad2/3 signaling pathway and autophagy.","authors":"Chunyan Zhang, Yabin Zhao, Haoyu Yan, Jianlin Guo, GuoYing Yu","doi":"10.1038/s41420-025-02694-4","DOIUrl":null,"url":null,"abstract":"<p><p>Liver fibrosis represents an important pathological stage during chronic hepatopathy development, posing a significant threat to human health. Hepatic stellate cells (HSCs), an essential hepatic non-parenchymal cells, have a key effect on fibrogenesis, with their activation being a hallmark of liver fibrosis. MicroRNAs (miRNAs), the small non-coding RNAs, become the critical biomarkers and regulatory molecules in fibrotic processes. Among them, miR-125a-5p is implicated in cancer and inflammatory pathways, yet its functional role and mechanistic involvement in HSC activation remain poorly understood. According to our findings, miR-125a-5p expression was significantly decreased in TGF-β-activated HSC-T6 cells. Notably, ectopic miR-125a-5p overexpression effectively inhibited TGF-β-mediated HSC-T6 activation. Further mechanistic investigations revealed that miR-125a-5p attenuated HSC activation while ameliorating liver fibrosis through regulating the TGF-β/Smad2/3 pathway and autophagy. Additionally, TGFβR1 was miR-125a-5p's target gene. Collectively, miR-125a-5p negatively regulates HSC activation in liver fibrosis, exerting its anti-fibrotic activities through suppressing the TGF-β/Smad2/3 pathway and autophagy modulation.</p>","PeriodicalId":9735,"journal":{"name":"Cell Death Discovery","volume":"11 1","pages":"419"},"PeriodicalIF":7.0000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12402229/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Death Discovery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41420-025-02694-4","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Liver fibrosis represents an important pathological stage during chronic hepatopathy development, posing a significant threat to human health. Hepatic stellate cells (HSCs), an essential hepatic non-parenchymal cells, have a key effect on fibrogenesis, with their activation being a hallmark of liver fibrosis. MicroRNAs (miRNAs), the small non-coding RNAs, become the critical biomarkers and regulatory molecules in fibrotic processes. Among them, miR-125a-5p is implicated in cancer and inflammatory pathways, yet its functional role and mechanistic involvement in HSC activation remain poorly understood. According to our findings, miR-125a-5p expression was significantly decreased in TGF-β-activated HSC-T6 cells. Notably, ectopic miR-125a-5p overexpression effectively inhibited TGF-β-mediated HSC-T6 activation. Further mechanistic investigations revealed that miR-125a-5p attenuated HSC activation while ameliorating liver fibrosis through regulating the TGF-β/Smad2/3 pathway and autophagy. Additionally, TGFβR1 was miR-125a-5p's target gene. Collectively, miR-125a-5p negatively regulates HSC activation in liver fibrosis, exerting its anti-fibrotic activities through suppressing the TGF-β/Smad2/3 pathway and autophagy modulation.

查看原文本刊更多论文

过表达miR-125a-5p通过TGF-β/Smad2/3信号通路和自噬抑制hsc活化，缓解肝纤维化。

肝纤维化是慢性肝病发展过程中的一个重要病理阶段，对人类健康构成重大威胁。肝星状细胞（HSCs）是一种重要的肝脏非实质细胞，在纤维化发生中起关键作用，其激活是肝纤维化的标志。MicroRNAs （miRNAs）是一种小的非编码rna，是纤维化过程中重要的生物标志物和调控分子。其中，miR-125a-5p与癌症和炎症通路有关，但其在HSC活化中的功能作用和机制参与尚不清楚。根据我们的发现，miR-125a-5p在TGF-β激活的HSC-T6细胞中表达显著降低。值得注意的是，异位miR-125a-5p过表达可有效抑制TGF-β介导的HSC-T6活化。进一步的机制研究表明，miR-125a-5p通过调节TGF-β/Smad2/3通路和自噬来减弱HSC活化，同时改善肝纤维化。此外，TGFβR1是miR-125a-5p的靶基因。总之，miR-125a-5p负调控肝纤维化中HSC的激活，通过抑制TGF-β/Smad2/3通路和自噬调节发挥其抗纤维化活性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

8.30

自引率

1.40%

发文量

468

审稿时长

9 weeks

期刊介绍： Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.