Androgen receptor ameliorates cardiomyocyte senescence through autophagy modulation: a mechanistic study
10.3760/cma.j.issn.0254-9026.2025.08.017
- VernacularTitle:睾酮受体通过调节自噬改善心肌细胞衰老及机制研究
- Author:
Rui TAN
1
;
Ying WANG
;
Peng YANG
;
Shuxun YAN
Author Information
1. 郑州大学第一附属医院老年心血管科，郑州 450052
- Publication Type:Journal Article
- Keywords:
Androgen receptor;
Senescence;
Cardiomyocytes;
Autophagy
- From:
Chinese Journal of Geriatrics
2025;44(8):1122-1130
- CountryChina
- Language:Chinese
-
Abstract:
Objective:This study aims to investigate the effect of androgen receptor(AR)on doxorubicin(DOX)-induced cardiomyocyte senescence and autophagy.Methods:H9C2 cardiomyocytes were cultured in vitro, and treated with 0.1 μM DOX for 48 hours to construct an aging cardiomyocytes model.An AR-overexpressing cardiomyocyte model was generated via adenovirus transfection.The cells were divided into four groups: Control group, Control+ AR-overexpression group, DOX group and DOX+ AR-overexpression group.Senescence-associated β-galactosidase staining was performed to assess the positive rate of β-galactosidase staining in myocardial cells; RT-PCR technology was used to detect the mRNA expression levels of senescence-related genes( P21, P53, IL-1 β, IL-6, MCP-1), the inflammasome NLRP3, and autophagy regulatory genes( TFEB and P62)in cardiomyocytes; the Western blot method was used to detect the protein expression levels of P21, AR, TFEB, P62, LC3-Ⅰ, LC3-Ⅱ, and the LC3-Ⅱ/LC3-Ⅰ ratio. Results:Compared with the Control group, the DOX group exhibited a significantly increased positive rate of SA-β-gal staining in myocardial cells( P<0.001). The mRNA expression of P21, P53, IL-1 β, IL-6, MCP-1, and NLRP3 were upregulated(all P<0.05), accompanied by elevated P21 protein expression( P<0.05), while the AR protein expression was downregulated( P<0.05). The LC3-Ⅱ/LC3-Ⅰ ratio was increased significantly( P<0.01), whereas both mRNA and protein expression levels of TFEB and P62 were reduced( P<0.05). Compared with the DOX group, the DOX+ AR-overexpression group exhibited a significantly reduced positive rate of SA-β-gal staining in myocardial cells( P<0.000 1), a decrease in P21 protein expression( P<0.05), a decrease in LC3-Ⅱ/LC3-Ⅰ ratio( P<0.01), and an increase in TFEB and P62 protein expression levels( P<0.05). Conclusions:AR enhances the autophagic clearance function of aging myocardial cells and inhibits cell aging phenotype through upregulating the expression levels of TFEB and P62.
