Effects of CXCR4 DNA Methylation Remodeled by TET2 on Autophagy,Inflammation and Apoptosis of Myocardial Tissue in Mice with Acute Myocardial Infarction
MAO Shan
ZHOU Ming
DUAN Banyan
CAO Zheng
LI Jun
Abstract：Objective:To explore the effect of tet methylcytosine dioxygenase 2(TET2)on DNA methylation of C-X-C motif receptor 4(CXCR4)during acute myocardial infarction(AMI),and the mechanism of its effect on myocardial autophagy,inflammation and apoptosis in AMI mice.Methods:Fifty 8-week-old male C57/BL6 mice AMI model were prepared,TET2 and CXCR4 overexpressing plasmids were injected into the tail.The expressions of TET2,CXCR4,microtubule associated protein 3(LC3),P62,B-cell lymphoma/leukemia-2 gene(Bcl-2)associated X protein(Bax),Caspase-3,and Bcl-2 in cardiac tissue were detected by Western Blot.The methylation level of CXCR4 DNA was detected.The levels of inflammatory factors interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)in myocardial tissue were detected by enzyme-linked immunosorbent assay(ELISA).Terminal deoxyribonucleotidyl transferase(TdT)-mediated dUTP nick end labeling(TUNEL)was used to detect apoptosis index of myocardial tissue in each group.Results:Compared with sham operation group,the expressions of TET2 and CXCR4 up-regulated in myocardial tissue of model group,and both TET2 and CXCR4 overexpressed in myocardial tissue,and overexpression of TET2 promoted CXCR4 expression(P<0.05).Compared with model group,DNA methylation of CXCR4 promoter region decreased and CXCR4 protein expression increased in TET2 mimic group(P<0.05).Compared with sham operation group,expressions of autophagy protein LC3 and apoptosis inhibiting protein Bcl-2 down-regulated in myocardial tissue of mice in model group,and levels of inflammatory factors IL-6,TNF-α,IL-1β,autophagy protein P62,pro-apoptotic protein Bax,cleaved Caspase-3 up-regulated(P<0.05).Overexpression of TET2 and CXCR4 further down-regulated the expression of LC3 and Bcl-2 proteins,up-regulated the levels of inflammatory factors IL-6,TNF-α,IL-1β,and expression of P62,Bax,cleaved Caspase-3 proteins.TET2 and CXCR4 showed the lowest LC3 and Bcl-2 protein expression,the highest inflammatory factors IL-6,TNF-α,IL-1βlevels,P62,Bax,cleaved Caspase-3 protein expression(P<0.05).Conclusion:In the development of AMI,TET2 can promote CXCR4 gene expression by reducing CXCR4 DNA methylation,thereby inhibiting myocardial autophagy in AMI mice,up-regulating inflammatory response and apoptosis,and promoting the development of the disease.
Keywords：acute myocardial infarctiontet methylcytosine dioxygenase 2C-X-C motif receptor 4DNA methylationautophagyinflammatory responseapoptosis
Publication Date：2024-05-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 1579-1584 )