JMJD2A mediates transcriptional activation of SFRP4 and regulates oxidative stress and mitochondrial dysfunction in heart failure

Ren, Mingming1; Ye, Xiaoqiang1; Ouyang, Chun1; Da, Qing'en1; Xue, Weiwei1; Chen, Piji2,3

2024-04-01

10.1111/pin.13413

PATHOLOGY INTERNATIONAL   影响因子和分区

1320-5463

1440-1827

The importance of mitochondrial dysfunction and oxidative stress has been indicated in the progression of heart failure (HF). The molecular mechanisms, however, remain to be fully elucidated. This study aimed to explore the role and underlying mechanism of secreted frizzled-related protein 4 (SFRP4) in these two events in HF. Mice with HF were developed using transverse aortic constriction, and hematoxylin-eosin staining, MASSON staining, and Terminal deoxynucleotidyl transferase (TdT)-mediated 2'-Deoxyuridine 5'- Triphosphate nick end labeling (TUNEL assays) were conducted to detect morphological damage in the myocardial tissues of mice. HL-1 mouse cardiomyocytes were induced with isoproterenol (ISO), and cell viability and apoptosis were examined using cell counting kit-8 and TUNEL assays. SFRP4 and Jumonji domain-containing protein 2A (JMJD2A) were highly expressed in myocardial tissues. Suppression of SFRP4 alleviated apoptosis and fibrosis in myocardial tissues of mice. In addition, the extent of mitochondrial dysfunction and oxidative stress in damaged myocardial tissues and HL-1 cells was mitigated by SFRP4 inhibition as well. JMJD2A catalyzed demethylation modification of the SFRP4 promoter, thus promoting SFRP4 transcription in the development of HF. JMJD2A is responsible for SFRP4 transcription activation in the failing hearts of mice. Blockade of JMJD2A or SFRP4 might be a novel therapy effective in mitigating HF progression.

heart failure JMJD2A mitochondrial dysfunction oxidative stress SFRP4

SCI

英语

通讯

Pathology

Pathology

WOS:001173626100001

WILEY

CLINICAL MEDICINE

Web of Science

1.Peking Univ, Shenzhen Hosp, Dept Cardiovasc Surg, Shenzhen, Guangdong, Peoples R China
2.Southern Univ Sci & Technol, Yantian Peoples Hosp, Dept Clin Lab, Shenzhen, Guangdong, Peoples R China
3.Southern Univ Sci & Technol, Yantian Peoples Hosp, Dept Clin Lab, 2010 Wutong Rd, Shenzhen 518083, Guangdong, Peoples R China

Ren, Mingming,Ye, Xiaoqiang,Ouyang, Chun,et al. JMJD2A mediates transcriptional activation of SFRP4 and regulates oxidative stress and mitochondrial dysfunction in heart failure[J]. PATHOLOGY INTERNATIONAL,2024,74(4).

Ren, Mingming,Ye, Xiaoqiang,Ouyang, Chun,Da, Qing'en,Xue, Weiwei,&Chen, Piji.(2024).JMJD2A mediates transcriptional activation of SFRP4 and regulates oxidative stress and mitochondrial dysfunction in heart failure.PATHOLOGY INTERNATIONAL,74(4).

Ren, Mingming,et al."JMJD2A mediates transcriptional activation of SFRP4 and regulates oxidative stress and mitochondrial dysfunction in heart failure".PATHOLOGY INTERNATIONAL 74.4(2024).