Fam172a基因敲除活化ERK通路加重肝细胞脂毒性损伤的研究  

ERK Pathway Activation by Fam172a Gene Knockdown Aggravates Lipotoxic Hepatocyte Injury

作　　者：李梦绮 韦何锐 罗婧 安稳 宋阿倩 何玲玲 杨君茹 魏红山 肖凡 LI Mengqi;WEI Herui;LOU Jing;AN Wen;SONG Aqian;HE Lingling;YANG Junru;WEI Hongshan;XIAO Fan(Department of Gastroenterology,Beijing Ditan Hospital,Capital Medical University,Beijing 100015,China;Department of Gastroenterology,Peking University Ditan Teaching Hospital,Beijing 100015,China;National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases,Beijing Ditan Hospital,Capital Medical University,Beijing,100015,China;Beijing Key Laboratory of Emerging Infectious Diseases,Institute of Infectious Diseases,Beijing Ditan Hospital,Capital Medical University,Beijing,100015,China;Beijing Institute of Infectious Diseases,Beijing,100015,China;National Center for Infectious Diseases,Beijing Ditan Hospital,Capital Medical University,Beijing,100015,China)

机构地区：[1]首都医科大学附属北京地坛医院消化科,北京市100015 [2]北京大学地坛医院教学医院消化科,北京市100015 [3]传染病溯源预警与智能决策全国重点实验室,首都医科大学附属北京地坛医院,北京市100015 [4]首都医科大学附属北京地坛医院传染病研究所,新发突发传染病研究北京市重点实验室,北京市100015 [5]北京市感染性疾病研究中心,北京市100015 [6]国家传染病医学中心,首都医科大学附属北京地坛医院,北京市100015

出　　处：《医学分子生物学杂志》2024年第6期501-507,共7页Journal of Medical Molecular Biology

基　　金：北京市自然科学基金(No.7202071);国家自然科学基金(No.82170541);国家自然科学基金(青年基金)(No.82200640)。

摘　　要：目的初步探讨Fam172a基因敲除加重脂毒性肝细胞损伤的作用机制。方法利用Fam172a基因敲除(Fam172a^(-/-))小鼠,检测肝功能、肝组织脂质堆积和炎症细胞因子水平。利用Fam172a基因敲减的HepG2细胞系,检测细胞内脂质堆积和炎症细胞因子水平。蛋白质印迹检测蛋白质水平。结果与对照组相比,Fam172a^(-/-)小鼠血浆ALT和AST水平明显升高;肝脏结构损伤、脂质堆积和炎症加重;pERK/ERK相对表达水平显著上调。Fam172a基因敲减后,HepG2细胞内甘油三酯含量和炎症细胞因子水平增加,且pERK/ERK相对表达水平也显著升高。然而,应用ERK抑制剂后可明显减轻Fam172a基因敲减造成的脂毒性肝细胞损伤。结论Fam172a基因敲除可通过活化ERK加重肝细胞脂毒性。Objective To preliminarily explore the mechanism of Fam172a gene knockout in lipid toxic liver cell injury.Method Fam172a gene knockout(Fam172a^(-/-))mice was used to assess liver function,liver tissue lipid accumulation,and inflammatory cytokine levels.Fam172a gene knockdown HepG2 cell lines were performed to assess intracellular lipid accumulation and inflammatory cytokine levels.Protein levels were analyzed via Western blotting.Results Compared to the control group,Fam172a^(-/-)mice exhibited significantly elevated serum ALT and AST levels,aggravated hepatic structural damage,lipid accumulation,and inflammation.Moreover,there was a significant upregulation in hepatic pERK/ERK relative expression levels.Fam172a gene knockdown led to increased triglyceride content and inflammatory cytokine levels in HepG2 cells,along with a significant elevation in the relative expression level of pERK/ERK.However,the administration of the ERK inhibitor U0126 notably mitigated the lipotoxic hepatocyte injury induced by Fam172a gene knockdown.Conclusion Fam172a gene knockdown exacerbates hepatocyte lipotoxicity through the activation of the ERK pathway.

关 键 词：Fam172a 细胞外调节蛋白激酶 脂毒性 非酒精性脂肪肝 

分 类 号：R349.6[医药卫生—基础医学]