FAK-TRIM25通过FBXW7抑制c-Myc泛素化促进HSC活化和糖酵解。

IF 5.9 2区医学 Q1 MEDICAL LABORATORY TECHNOLOGY

Translational Research Pub Date : 2026-03-01 Epub Date: 2026-02-14 DOI:10.1016/j.trsl.2026.02.005

Lu Han , Guo-Yuan Lin , Shao-Jie Chen , Qing-Xiu Zhang , Hua-Yue Wu , Tao Huang , Fan Lu , Hong-Fei Pu , Jing-Lin Wang , Tao Ran , Gao-Liang Zou , Jian-Chao Li , Ya Zhang , Xue-Ke Zhao

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引用次数: 0

摘要

肝纤维化的特征是肝星状细胞（HSC）激活和葡萄糖消耗增加。Focal adhesion kinase （FAK）上调造血干细胞中c-Myc的表达，促进有氧糖酵解。本研究探讨FAK如何通过TRIM25促进HSC活化和糖酵解。免疫组织化学（IHC）和Western blotting检测FAK、TRIM25、FBXW7、c-Myc和糖酵解相关蛋白在人肝组织和小鼠模型中的表达。通过共免疫沉淀（Co-IP）和LC-MS鉴定蛋白相互作用，通过免疫荧光观察FAK和TRIM25的定位。FAK抑制降低了LX-2细胞的活化、迁移和糖酵解。Co-IP和免疫荧光证实FAK-TRIM25相互作用。FAK抑制fbxw7介导的c-Myc泛素化，并通过结合TRIM25的RING、B-BOX和SPRY区域增强糖酵解。抑制FAK可改善肝纤维化和糖酵解。FAK通过TRIM25相互作用促进HSC糖酵解，其抑制作用减轻肝纤维化，提示潜在的治疗靶点。

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FAK-TRIM25 promotes HSC activation and glycolysis by inhibiting c-Myc ubiquitination via FBXW7

Liver fibrosis is marked by hepatic stellate cell (HSC) activation and increased glucose consumption. Focal adhesion kinase (FAK) upregulates c-Myc expression in HSCs, promoting aerobic glycolysis. This study explores how FAK promotes HSC activation and glycolysis via TRIM25. Immunohistochemistry (IHC) and Western blotting assessed the expression of FAK, TRIM25, FBXW7, c-Myc, and glycolysis-related proteins in human liver tissues and mouse models. Protein interactions were identified by co-immunoprecipitation (Co-IP) and LC-MS, and FAK and TRIM25 localization was observed by immunofluorescence. FAK inhibition reduced LX-2 cell activation, migration, and glycolysis. Co-IP and immunofluorescence confirmed FAK-TRIM25 interaction. FAK inhibits FBXW7-mediated c-Myc ubiquitination and enhances glycolysis by binding TRIM25’s RING, B-BOX, and SPRY regions. Inhibition of FAK improved liver fibrosis and glycolysis. FAK promotes HSC glycolysis through TRIM25 interaction, and its inhibition mitigates liver fibrosis, suggesting a potential therapeutic target.

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来源期刊

Translational Research 医学-医学：内科

CiteScore

15.70

自引率

0.00%

发文量

195

审稿时长

14 days

期刊介绍： Translational Research (formerly The Journal of Laboratory and Clinical Medicine) delivers original investigations in the broad fields of laboratory, clinical, and public health research. Published monthly since 1915, it keeps readers up-to-date on significant biomedical research from all subspecialties of medicine.