Ultraviolet resistance-associated gene (Uvrag) deficiency promotes cellular senescence in the heart

doi:10.3969/j.issn.2095-4344.3126

Abstract

Abstract: BACKGROUND: Previously we have shown that ultraviolet resistance-associated gene (Uvrag) deficient mice develop age-related cardiomyopathy. However, whether cellular senescence contributes to the pathogenesis remains unknown.
OBJECTIVE: To determine cellular senescence in Uvrag-deficient hearts.
METHODS: Wild-type and Uvrag-deficient male mice at 3 and 8 months of age were utilized. Real-time RT-PCR was used to detect the changes in the mRNA expression of senescence-associated secretory phenotype-related factors in mouse heart tissue, and myocardial histological observation was performed using hematoxylin-eosin staining, Sirius scarlet staining, and aging-related β-galactosidase staining. Transmission electron microscopy was used to observe the ultrastructure changes of mouse cardiomyocytes. Western blot was used to detect the expression of p53 protein in mouse heart tissue. An approval was obtained from the Experimental Animal Ethics Committee of Shanghai Jiaotong University.
RESULTS AND CONCLUSION: Hematoxylin-eosin staining and Sirius red staining showed that cross-sectional area of individual cardiomyocytes was enlarged and cardiac fibrosis was enhanced in the Uvrag-deficient mice. In addition, cardiomyocytes in the Uvrag-deficient mice exhibited abnormal mitochondrial morphology, disordered arrangement, and swollen sarcoplasmic reticulum as revealed by transmission electron microscopy. Senescence-associated ß-galactosidase staining suggested that Uvrag deficiency significantly increased senescent cells in the hearts from Uvrag-deficient mice. Furthermore, real-time RT-PCR demonstrated a marked increase in the expression of the senescence-associated secretory phenotype genes in Uvrag-deficient hearts. Finally, western blot showed that the expression of p53, a key regulator of cellular senescence, was upregulated in Uvrag-deficient hearts. To conclude, Uvrag deficiency promotes cellular senescence in the mouse heart. Uvrag is a potential target for delaying senescence of the heart and anti-aging-related heart disease.

Key words: heart, gene, Uvrag, senescence, cellular senescence, age-related secretory phenotype, p53, autophagy

CLC Number:

Lai Shuaiwei, Zhang Shasha, Liu Xiaoyun, Haniya Mazhar, Amber Naz, He Lin, Zhu Hongxin. Ultraviolet resistance-associated gene (Uvrag) deficiency promotes cellular senescence in the heart[J]. Chinese Journal of Tissue Engineering Research, 2021, 25(14): 2241-2246.

Figures/Tables 5

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