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Review
. 2022 Sep 13:14:933015.
doi: 10.3389/fnagi.2022.933015. eCollection 2022.

DNA damage response and GATA4 signaling in cellular senescence and aging-related pathology

Hao Xiong  1   2 , Fuzhou Hua  1   2 , Yao Dong  3 , Yue Lin  1   2 , Jun Ying  1   2 , Jie Liu  1   2 , Xifeng Wang  3 , Lieliang Zhang  1   2 , Jing Zhang  1
Affiliations
Review

DNA damage response and GATA4 signaling in cellular senescence and aging-related pathology

Hao Xiong et al. Front Aging Neurosci. .

Abstract

Aging is the continuous degradation of biological function and structure with time, and cellular senescence lies at its core. DNA damage response (DDR) can activate Ataxia telangiectasia-mutated serine/threonine kinase (ATM) and Rad3-related serine/threonine kinase (ATR), after which p53 activates p21, stopping the cell cycle and inducing cell senescence. GATA4 is a transcription factor that plays an important role in the development of many organs, such as the heart, testis, ovary, foregut, liver, and ventral pancreas. Studies have shown that GATA4 can also contribute to the DDR, leading to aging. Consistently, there is also evidence that the GATA4 signaling pathway is associated with aging-related diseases, including atherosclerosis and heart failure. This paper reviews the relationship between GATA4, DDR, and cellular senescence, as well as its effect on aging-related diseases.

Keywords: CGATA4; DNA damage response; atherosclerosis; cellular senescence; heart failure.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The role of GATA4 in atherosclerosis and myocardial hypertrophy. The GATA4-TWIST1-Snail signaling pathway promotes EC dysfunction and atherosclerosis. GATA4 may regulate cell hypertrophy by increasing the expression level of GATA4, DNA binding activity, and transcriptional activity under the stimulation of the hypertrophy signal.
Figure 2
Figure 2
The process of DNA damage leading to cell senescence and the role of GATA4 in it. DNA damage signals activate ATM and ATR, causing the p53 and p16 pathways to activate, blocking cell cycles and, in turn, aging cells. ATM and ATR can also suppress selective autophagy between p62 and GATA4, activating NF-κB and SASP.
Figure 3
Figure 3
The role of GATA4 in various organs and aging-related diseases. GATA4 can promote the development of heart, testis, ovary, foregut, liver, and ventral pancreas and can lead to heart disease associated with aging.
See this image and copyright information in PMC

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