Alleviation of cardiomyocyte senescence by silent information regulator 6 through up-regulating FOXM1/Wnt/β-catenin signaling pathway
MA Yongxiang
SHEN Jing
LU Zhenhua
ZHANG Jing
NIU Lijian
HUANG Wenjun
Abstract：Objective To investigate the influence of silent information regulator 6(SIRT6)on cardiomyocyte senescence induced by D-galactose(D-gal)through regulating forkhead box M1(FOXM1)/Wnt/β-catenin signaling pathway.Methods H9c2 cardiomyocytes were divided into Control group,D-gal group,D-gal+pcDNA3.1-NC group,D-gal+pcDNA3.1-SIRT6 group,D-gal+shRNA NT group and D-gal+SIRT6 shRNA group.The cell viability was detected by cell counting kit-8(CCK-8).The cell senescence was detected by β-galactosidase(SA-β-Gal)staining.The content of reactive oxygen species(ROS)was detected by DCFH-DA fluorescence probe assay.The changes of mitochondrial membrane potential(MMP)were detected by JC-1 staining.The mRNA expressions of SIRT6,p16 and p21 were detected by qRT-PCR.The protein expressions of SIRT6 protein and FOXM1/Wnt/β-catenin signaling pathway were detected by Western blotting assay.Results Compared with the D-gal group,the cell viability increased significantly in pcDNA3.1-SIRT6 group[(73.2±1.8)%vs.(88.7±1.1)%,P<0.05],and decreased significantly in D-gal+SIRT6 shRNA group[(73.2±1.8)%vs.(55.6±0.9)%,P<0.05].Compared with D-gal group,the intracellular MMP increased significantly[(96.2±3.8)%vs.(145.6±4.3)%,P<0.05],cardiomyocyte senescence rate decreased significantly[(57.4±1.1)%vs.(28.3±0.7)%,P<0.05],relative expressions of p16 mRNA[(1.83±0.14)vs.(1.34±0.09)]and p21 mRNA[(2.26±0.18)vs.(1.62±0.13)]decreased significantly(P<0.05),and ROS level[(786.5±4.4)vs.(422.8±3.6),P<0.050]decreased significantly in D-gal+pcDNA3.1-SIRT6 group.Compared with D-gal group,the relative expressions of FOXM1 protein[(0.44±0.03)vs.(0.72±0.06)]and Wnt3α protein[(0.51±0.04)vs.(0.76±0.05)]and ratio of p-β-catenin/β-catenin[(0.21±0.02)vs.(0.52±0.05)]significantly increased in pcDNA3.1-SIRT6 group(P<0.05).Conclusion SIRT6 may alleviate oxidative stress,mitochondrial damage and cellular senescence in cardiomyocytes by upregulating FOXM1/Wnt3α/β-catenin signaling pathway.
Keywords：silent information regulator 6cardiomyocytesenescenceD-galactoseoxidative stressmitochondrion function
Publication Date：2025-11-20
Online Publishing Date：2026-03-25(First online date of this platform, not the publication date of the document)
Pages：6( 1307-1312 )