实验性2型糖尿病小鼠肝脏组蛋白H3表观修饰的变化及其意义

doi:10.13481/j.1671-587x.20150417

Abstract

Abstract:

Objective To study the role of liver total histone epigenetic modification changes in the development of type 2 diabetes mellitus in the mice,and to explore its clinical significance. Methods Thirty C57BL/6J mice were divided into normal group,high-fat high-sucrose (HFS) group and type 2 diabetes mellitus (T2DM) group.The mice in normal and HFS groups were given regular diet and HFS diet,respectively,while type 2 diabetic mice were induced by HFS diet plus streptozotocin (STZ).HE staining,Western blotting,Quantitative PCR and ChIP assay were used to analyze the pathological changes of liver tissue of the mice,total histone H3 modification,the expression levels of glucose metabolism-related genes and histone H3 modification in gene promoter. Results The liver pathology after HE staining and modification patterns of histone of the mice in T2DM group were significantly different from other groups.Compared with normal group,the H3K23 acetylation of the mice in HFS group was decreased (P<0.01),the modification levels of H3K9Ac and H3K9Me2 were increased (P<0.01),the level of H3K4Me had no change (P>0.05),and the expression levels of glucose metabolism-related genes Pklr,Glut2 and Gck were increased (P<0.01). Compared with normal group,the modification levels of H3K23Ac (P<0.01) and H3K9Ac (P<0.05) in T2DM group were decreased, the modification levels of H3K9Me2 and H3K4Me were increased (P<0.01),and the expression levels of glucose metabolism-related genes Pklr,Glut2,Gck,Ppargc1a and Insr were decreased (P<0.05 or P<0.01).Moreover,the changes of H3K23Ac,H3K9Ac,H3K9Me2 and H3K4Me modification in gene promoter of Glut2 and Pklr showed consistent with its expression levels. Conclusion The epigenetic modification changes of liver histone might participate in the occurrence and development of type 2 diabetes mellitus.

Key words: type 2 diabetes mellitus, epigenetics, histone H3, pyruvate kinase, glucose transporter protein 2

CLC Number:

R589.1

TU Peipei, LI Xiaodan, MA Baicheng, ZHANG Yaofang, DUAN Huikun, NI Zaizhong, WANG Haisong, JIANG Pingzhe, LI Miao, WU Ri, LI Minggang. Changes and significance of hepatic histone H3 epigenetic modification in type 2 diabetic mice[J].Journal of Jilin University Medicine Edition, 2015, 41(04): 756-762.

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Changes and significance of hepatic histone H3 epigenetic modification in type 2 diabetic mice

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