湖北科技学院学报(医学版)2026,Vol.40Issue(4):321-326,6.DOI:10.16751/j.cnki.2095-4646.2026030507
KDM5B通过自噬影响肝纤维化的作用及机制研究
Study on the Role and Mechanism of KDM5B in Liver Fibrosis via Autophagy
摘要
Abstract
Objective To investigate the expression characteristics of the histone demethylase KDM5B in liver fibrosis,as well as the role and mechanism by which it influences the activation of hepatic stellate cells(HSCs)through the regulation of autophagy.Methods CCl4-induced mouse hepatic fibrosis model was established,and the TGF-β1-activated human hepatic stellate cell line(LX-2)was used as the in vitro model.qRT-PCR,Western blot,and immunohistochemistry were performed to detect the expression and localization of KDM5B.After administration of the KDM5B inhibitor AS-8351,hepatic collagen deposition,serum alanine aminotransferase(ALT)and aspartate ami-notransferase(AST)levels were observed,and the expression levels of autophagy-related proteins LC3-Ⅱ/l,Beclin-1 and SQSTM1(p62)were evaluated.Results KDM5B was significantly upregulated in both fibrotic liver tissues and activated LX-2 cells.After intervention with the KDM5B inhibitor AS-8351,collagen deposition was markedly reduced,serum ALT and AST levels were decreased,the expression of LC3-Ⅱ/l and Beclin-1 was downregulated,and the accumulation of SQSTM1(p62)was increased,indicating the blockade of autophagic flux.Conclusion Elevated KDM5B expression is significantly correlated with autophagy activation,HSC activation and hepatic fibrosis progres-sion.Inhibiting KDM5B significantly suppresses autophagy and alleviates hepatic fibrosis progression,offering a novel therapeutic target for the treatment of hepatic fibrosis.关键词
KDM5B/自噬/肝纤维化/肝星状细胞Key words
KDM5B/Autophagy/Liver fibrosis/Hepatic stellate cells分类
医药卫生引用本文复制引用
马谣谣,欧浩翔,阙鑫宇,黄文涛,肖嘉琪,黄翠萍,瞿利花,单士刚,郭艺..KDM5B通过自噬影响肝纤维化的作用及机制研究[J].湖北科技学院学报(医学版),2026,40(4):321-326,6.基金项目
湖北省自然科学基金(2024AFB517) (2024AFB517)
湖北科技学院发展基金项目(BK202442) (BK202442)
湖北科技学院"糖尿病与血管病变专项"基金(2024TNB05) (2024TNB05)