SOX4 as a potential therapeutic target for pathological cardiac hypertrophy

Shen Bin; Feng Xinyi; Pan Huan; Zhang Xiaoqin; Wu Jiming; He Yi; Li Ziyue; Zou Xiaochun; Lu Zhouqi; Zhou Bangwei; Jin Jing; Liu Shihui; Gao Jinlai

doi:10.1016/j.ejphar.2023.176071

SOX4 as a potential therapeutic target for pathological cardiac hypertrophy

Eur J Pharmacol. 2023 Nov 5:958:176071. doi: 10.1016/j.ejphar.2023.176071. Epub 2023 Sep 21.

Authors

Shen Bin¹, Feng Xinyi¹, Pan Huan², Zhang Xiaoqin¹, Wu Jiming¹, He Yi³, Li Ziyue¹, Zou Xiaochun¹, Lu Zhouqi¹, Zhou Bangwei¹, Jin Jing⁴, Liu Shihui⁵, Gao Jinlai⁶

Affiliations

¹ Department of Pharmacology, College of Medical, Jiaxing University, Jiaxing, 314000, China.
² Department of Central Laboratory, The Affiliated Hospital of Jiaxing University, Jiaxing, 314000, China.
³ Department of Central Laboratory, The Affiliated Hospital of Jiaxing University, Jiaxing, 314000, China; Department of Urology, The Affiliated Hospital of Jiaxing University, Jiaxing, 314000, China.
⁴ Department of Urology, The Affiliated Hospital of Jiaxing University, Jiaxing, 314000, China. Electronic address: jinjing@zjxu.edu.cn.
⁵ Department of Pharmacology, College of Medical, Jiaxing University, Jiaxing, 314000, China. Electronic address: liushihui12310@zjxu.edu.cn.
⁶ Department of Pharmacology, College of Medical, Jiaxing University, Jiaxing, 314000, China. Electronic address: gaojinlai@zjxu.edu.cn.

PMID: 37741429
DOI: 10.1016/j.ejphar.2023.176071

Abstract

Pathological cardiac hypertrophy can lead to heart failure, making its prevention crucial. SOX4, a SOX transcription factor, regulates tissue growth and development, although its role in pathological cardiac hypertrophy is unclear. We found that the SOX4 expression was elevated in hypertrophic hearts and angiotensin II (Ang II)-treated neonatal rat cardiomyocytes (NRCMs), and knocking down the SOX4 expression in NRCMs and mouse hearts significantly reduced the hypertrophic response. Mechanistically, SOX4 can bind to the SIRT3 promoter, inhibit SIRT3 transcription and expression, and thus affect downstream MnSOD acetylation levels, leading to abnormal increases in ROS and oxidative stress levels and promoting the occurrence of cardiac hypertrophy. In conclusion, this study identified a new role for SOX4 in regulating cardiac hypertrophy, and decreasing SOX4 expression may be a potential treatment for pathological cardiac hypertrophy.

Keywords: Pathological cardiac hypertrophy; SIRT3; SOX4.

MeSH terms

Angiotensin II / metabolism
Animals
Cardiomegaly / metabolism
Heart Failure* / pathology
Mice
Myocytes, Cardiac / metabolism
Rats
SOXC Transcription Factors* / metabolism
Sirtuin 3* / metabolism

Substances

Angiotensin II
Sirtuin 3
Sox4 protein, mouse
SOXC Transcription Factors