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BRG1 Deficiency Promotes Cardiomyocyte Inflammation and Apoptosis by Activating the cGAS-STING Signaling in Diabetic Cardiomyopathy.
Chen, Ziying; Lai, Xiangmao; Li, Jingxuan; Yuan, Xun; Li, Yilang; Zhang, Xiaojing; Kang, Zhanfang; Ouyang, Zizhang; Zeng, Jianwen; Hou, Ning; Liu, Xiaoping.
Afiliación
  • Chen Z; Department of Pharmacy, Affiliated Qingyuan Hospital, Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan 511518, China.
  • Lai X; Guangdong Key Laboratory of Molecular Target & Clinical Pharmacology, the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, China.
  • Li J; Department of Urology, Affiliated Qingyuan Hospital, Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, 511518, China.
  • Yuan X; Guangdong Engineering Technology Research Center of Urinary Continence and Reproductive Medicine, Guangzhou Medical University, Qingyuan, 511518, China.
  • Li Y; Department of Pharmacy, Affiliated Qingyuan Hospital, Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan 511518, China.
  • Zhang X; Guangdong Key Laboratory of Molecular Target & Clinical Pharmacology, the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, China.
  • Kang Z; Guangdong Key Laboratory of Molecular Target & Clinical Pharmacology, the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, China.
  • Ouyang Z; Guangdong Key Laboratory of Molecular Target & Clinical Pharmacology, the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences and the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, China.
  • Zeng J; Department of Pharmacy, Affiliated Qingyuan Hospital, Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan 511518, China.
  • Hou N; Guangdong Engineering Technology Research Center of Urinary Continence and Reproductive Medicine, Guangzhou Medical University, Qingyuan, 511518, China.
  • Liu X; Department of Basic Medical Research, Affiliated Qingyuan Hospital, Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, 511518, China.
Inflammation ; 2024 Jun 13.
Article en En | MEDLINE | ID: mdl-38867118
ABSTRACT
Brahma-related gene 1 (BRG1) has been implicated in the repair of DNA double-strand breaks (DSBs). Downregulation of BRG1 impairs DSBs repair leading to accumulation of double-stranded DNA (dsDNA). Currently, the role of BRG1 in diabetic cardiomyopathy (DCM) has not been clarified. In this study, we aimed to explore the function and molecular by which BRG1 regulates DCM using mice and cell models. We found that BRG1 was downregulated in the cardiac tissues of DCM mice and in cardiomyocytes cultured with high glucose and palmitic acid (HG/PA), which was accompanied by accumulation of dsDNA and activation of the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway. shRNA-mediated Brg1 knockdown aggravated DCM mice cardiac functions, enhanced dsDNA accumulation, cGAS-STING signaling activation, which induced inflammation and apoptosis. In addition, the results were further verified in HG/PA-treated primary neonatal rat cardiomyocytes (NRCMs). Overexpression of BRG1 in NRCMs yielded opposite results. Furthermore, a selective cGAS inhibitor RU.521 or STING inhibitor C-176 partially reversed the BRG1 knockdown-induced inflammation and apoptosis in vitro. In conclusion, our results demonstrate that BRG1 is downregulated during DCM in vivo and in vitro, resulting in cardiomyocyte inflammation and apoptosis due to dsDNA accumulation and cGAS-STING signaling activation. Therefore, targeting the BRG1-cGAS-STING pathway may represent a novel therapeutic strategy for improving cardiac function of patients with DCM.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Inflammation Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Inflammation Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos