Study of Dapagliflozin on the promotion of mitochondrial autophagy in cardiomyocytes of diabetic cardiomyopathy by the regulation of TOM20 expression
10.3969/j.issn.1006-6187.2025.07.008
- VernacularTitle:达格列净通过调控线粒体外膜转运酶20表达促进糖尿病性心肌病心肌细胞线粒体自噬的研究
- Author:
Weiyi WANG
1
;
Yi WU
1
;
Jingqi ZHANG
1
;
Lu FU
1
Author Information
1. 150001 哈尔滨医科大学附属第一医院心内科
- Publication Type:Journal Article
- Keywords:
SGLT2 inhibitors;
Mitochondrial outer membrane transportase 20;
Diabetic cardiomyopathy;
Mitochondrial autophagy
- From:
Chinese Journal of Diabetes
2025;33(7):518-527
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effect of SGLT2 inhibitor(SGLT2i)Dagaglipzin(Dap)on mitochondrial autophagy in cardiomyocytes in diabetic cardiomyopathy(DCM)by regulating mitochondrial membrane transporter TOM20.Methods H9C2 cardiomyocytes cultured in vitro were divided into normal control(Con)group,HG+PA group,knockout TOM20(HG+PA+siTOM20)group,knockout control(HG+PA+siNC)group,Dap intervention(HG+PA+Dap)group,and solvent control(HG+PA+DMSO)group.The expression of TOM20 was predicted by RNA-seq second-generation sequencing in HG+PA group.The expression of TOM20 and mitochondrial autophagy related proteins was detected by Western blot,the mitochondrial membrane potential was measured by immunofluorescence staining,and the mitochondrial autophagy level was evaluated by transmission electron microscopy.Results Compared with Con group,protein expressions of TOM20 and P62 were increased(P<0.05),while protein expressions of ULK1,Parkin,Beclin1 and LC3-B were decreased(P<0.05),mitochondrial membrane potential was destroyed,the number of mitochondrial autophagosomes was reduced,and autophagy activity was inhibited in HG+PA group.Compared with HG+PA+siNC group and HG+PA+DMSO group,the protein expressions of TOM20 and P62 were decreased(P<0.05),while the protein expressions of ULK1,Parkin,Beclin1 and LC3-B were increased(P<0.05),the damage of mitochondrial membrane potential decreased,the number of mitochondrial autophagosomes increased,and the inhibition of autophagy activity reversed in HG+PA+siTOM20 and HG+PA+DAPA groups.Conclusions SGLT2 inhibitors appear to partially restore mitochondrial function in diabetic cardiomyopathy by suppressing TOM20 expression,potentially through activation of mitochondrial autophagy.
