过表达丝裂原诱导基因6通过抑制内质网应激减少棕榈酸诱导的肝细胞脂质蓄积
R363.2%R575%Q591.5; 目的:探讨过表达丝裂原诱导基因6(MIG6)通过调节肝细胞内质网应激影响棕榈酸(PA)诱导的肝细胞脂肪变性的作用及其机制.方法:通过使用高脂饲料喂养20只C57BL/6J小鼠26周构建小鼠非酒精性脂肪性肝炎模型,将小鼠随机分为2组:普通饮食对照组和高脂饮食组,每组10只,留取其肝脏进行后续实验.使用PA诱导HepG2细胞和AML12细胞的脂质蓄积,将细胞分为2组:BSA(10%BSA)组和PA(500 μmol/L)组.通过给HepG2细胞和AML12细胞分别转染人和小鼠MIG6过表达质粒诱导肝细胞MIG6过表达,根据不同的干预条件分为4组:阴性对照质粒...
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| Published in | 中国病理生理杂志 Vol. 40; no. 7; pp. 1213 - 1221 |
|---|---|
| Main Authors | , , , |
| Format | Journal Article |
| Language | Chinese |
| Published |
南方医科大学顺德医院(佛山市顺德区第一人民医院),广东 佛山 528300
2024
中山大学附属第三医院,广东 广州 510630%中山大学附属第三医院,广东 广州 510630 |
| Subjects | |
| Online Access | Get full text |
| ISSN | 1000-4718 |
| DOI | 10.3969/j.issn.1000-4718.2024.07.008 |
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| Abstract | R363.2%R575%Q591.5; 目的:探讨过表达丝裂原诱导基因6(MIG6)通过调节肝细胞内质网应激影响棕榈酸(PA)诱导的肝细胞脂肪变性的作用及其机制.方法:通过使用高脂饲料喂养20只C57BL/6J小鼠26周构建小鼠非酒精性脂肪性肝炎模型,将小鼠随机分为2组:普通饮食对照组和高脂饮食组,每组10只,留取其肝脏进行后续实验.使用PA诱导HepG2细胞和AML12细胞的脂质蓄积,将细胞分为2组:BSA(10%BSA)组和PA(500 μmol/L)组.通过给HepG2细胞和AML12细胞分别转染人和小鼠MIG6过表达质粒诱导肝细胞MIG6过表达,根据不同的干预条件分为4组:阴性对照质粒+10%BSA(negative+BSA)组、MIG6过表达质粒+10%BSA(MIG6+BSA)组、阴性对照质粒+PA(negative+PA)组和MIG6过表达质粒+PA(MIG6+PA)组,每组每次干预至少设3个生物学复孔.使用油红O染色评估肝细胞脂质蓄积情况;通过RT-qPCR检测肝组织MIG6的mRNA表达水平,Western blot检测肝细胞MIG6、脂肪酸合酶(FASN)和胆固醇调节元件结合蛋白1(SREBP1)等脂质合成相关分子及内质网应激标志物葡萄糖调节蛋白78(GRP78)和C/EBP同源蛋白(CHOP)的蛋白水平.结果:高脂饮食组小鼠肝组织甘油三酯含量增加,肝组织脂肪变性显著,MIG6的mRNA表达水平显著下调(P<0.01);PA干预促使肝细胞FASN、SREBP1、GRP78和CHOP蛋白水平升高,但是降低MIG6蛋白水平(P<0.01).转染MIG6过表达质粒显著增加肝细胞MIG6蛋白水平,并抑制GRP78和CHOP的表达(P<0.01),显著减轻PA诱导的肝细胞脂质蓄积并抑制FASN和SREBP1的表达(P<0.01).以上结果表明过表达MIG6可抑制PA诱导的肝细胞内质网应激并减少其脂质蓄积.结论:过表达MIG6具有抑制内质网应激进而抑制肝细胞脂质蓄积的作用. |
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| AbstractList | R363.2%R575%Q591.5; 目的:探讨过表达丝裂原诱导基因6(MIG6)通过调节肝细胞内质网应激影响棕榈酸(PA)诱导的肝细胞脂肪变性的作用及其机制.方法:通过使用高脂饲料喂养20只C57BL/6J小鼠26周构建小鼠非酒精性脂肪性肝炎模型,将小鼠随机分为2组:普通饮食对照组和高脂饮食组,每组10只,留取其肝脏进行后续实验.使用PA诱导HepG2细胞和AML12细胞的脂质蓄积,将细胞分为2组:BSA(10%BSA)组和PA(500 μmol/L)组.通过给HepG2细胞和AML12细胞分别转染人和小鼠MIG6过表达质粒诱导肝细胞MIG6过表达,根据不同的干预条件分为4组:阴性对照质粒+10%BSA(negative+BSA)组、MIG6过表达质粒+10%BSA(MIG6+BSA)组、阴性对照质粒+PA(negative+PA)组和MIG6过表达质粒+PA(MIG6+PA)组,每组每次干预至少设3个生物学复孔.使用油红O染色评估肝细胞脂质蓄积情况;通过RT-qPCR检测肝组织MIG6的mRNA表达水平,Western blot检测肝细胞MIG6、脂肪酸合酶(FASN)和胆固醇调节元件结合蛋白1(SREBP1)等脂质合成相关分子及内质网应激标志物葡萄糖调节蛋白78(GRP78)和C/EBP同源蛋白(CHOP)的蛋白水平.结果:高脂饮食组小鼠肝组织甘油三酯含量增加,肝组织脂肪变性显著,MIG6的mRNA表达水平显著下调(P<0.01);PA干预促使肝细胞FASN、SREBP1、GRP78和CHOP蛋白水平升高,但是降低MIG6蛋白水平(P<0.01).转染MIG6过表达质粒显著增加肝细胞MIG6蛋白水平,并抑制GRP78和CHOP的表达(P<0.01),显著减轻PA诱导的肝细胞脂质蓄积并抑制FASN和SREBP1的表达(P<0.01).以上结果表明过表达MIG6可抑制PA诱导的肝细胞内质网应激并减少其脂质蓄积.结论:过表达MIG6具有抑制内质网应激进而抑制肝细胞脂质蓄积的作用. |
| Abstract_FL | AIM:To investigate the effects of mitogen-inducible gene 6(MIG6)overexpression on palmitic acid(PA)-induced endoplasmic reticulum stress-associated steatosis in hepatocytes.METHODS:A mouse model of non-alcoholic steatohepatitis was established by feeding twenty C57BL/6J mice a high-fat diet for 26 weeks.The mice were ran-domly divided into two groups:normal diet control group and high-fat diet group,and their livers were retained for subse-quent experiments.The PA was used to induce lipid accumulation in HepG2 cells and AML12 cells,and the cells were di-vided into two groups:BSA(10%BSA)group and PA(500 μmol/L PA)group.The MIG6 overexpression was induced by transfecting HepG2 and AML12 cells with human and mouse MIG6 overexpression plasmids,respectively.The cells were divided into four groups according to their different treatment conditions:(1)negatiive+BSA group(transfected with nega-tive control plasmid+10%BSA);(2)MIG6+BSA group(transfected with MIG6 overexpression plasmid+10%BSA);(3)negative+PA group(transfected with negative control plasmid+500 μmol/L PA);(4)MIG6+PA group(transfected with MIG6 overexpression plasmid+500 μmol/L PA).Lipid accumulation in hepatocytes was assessed by oil red O staining,and RT-qPCR was used to detect the mRNA expression level of MIG6 in liver tissues.The protein levels of MIG6,lipid synthesis-related molecules fatty acid synthase(FASN)and sterol regulatory element-binding protein 1(SREBP1),and endoplasmic reticulum stress-related proteins glucose regulated protein 78(GRP78)and C/EBP homologous protein(CHOP)in hepatocytes were detected using Western blot.RESULTS:High-fat diet increased the triglyceride content in the liver tissue of C57BL/6J mice induced lipid accumulation in hepatocytes and suppressed the mRNA expression level of MIG6(P<0.01).PA intervention increased the protein levels of lipid synthesis-related molecules such as FASN and SREBP1,and endoplasmic reticulum stress markers GRP78 and CHOP in hepatocytes,but inhibited MIG6 protein levels(P<0.01).We transfected hepatocytes with MIG6 overexpression plasmid,which significantly increased MIG6 protein levels,decreased GRP78 and CHOP protein levels in hepatocytes(P<0.01),significantly attenuated PA-induced lipid accumulation in hepatocytes,and down-regulated FASN and SREBP1 protein levels(P<0.01).These results indicate that MIG6 overexpression inhibited PA-induced endoplasmic reticulum stress and attenuated lipid accumulation in hepato-cytes.CONCLUSION:Overexpression of MIG6 inhibits lipid accumulation in hepatocytes by suppressing endoplasmic reticulum stress. |
| Author | 蔡梦茵 梁华 邓小杰 王甜 |
| AuthorAffiliation | 中山大学附属第三医院,广东 广州 510630%中山大学附属第三医院,广东 广州 510630;南方医科大学顺德医院(佛山市顺德区第一人民医院),广东 佛山 528300 |
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| Author_FL | DENG Xiaojie WANG Tian CAI Mengyin LIANG Hua |
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| DocumentTitle_FL | Overexpression of MIG6 reduces palmitic acid-induced lipid accumula-tion in hepatocytes by inhibiting endoplasmic reticulum stress |
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| Keywords | 丝裂原诱导基因6 非酒精性脂肪性肝病 nonalcoholic fatty liver disease 脂质蓄积 内质网应激 lipid accumulation mitogen-inducible gene 6 endoplasmic reticulum stress |
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| Title | 过表达丝裂原诱导基因6通过抑制内质网应激减少棕榈酸诱导的肝细胞脂质蓄积 |
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