Nuclear damage-induced DNA damage response coupled with IFI16-driven ECM remodeling underlies dilated cardiomyopathy

作者：Qingyong He, Xing Chang, Hui Zhang, Qianying Hao, Jianguo Zhi, Hongshuo Shi, Yingjie Tian, Hao Zhou, Ying Tan, Junmeng Zheng, Junxiong Qiu, Jun Tao · 发表于：Theranostics · 年份：2025 · DOI：10.7150/thno.112247 · 被引用次数：10 · 研究领域：Cardiac Fibrosis and Remodeling、Cardiomyopathy and Myosin Studies

Our findings delineate a novel pathogenic axis in DCM where nuclear stress-induced DDR activation drives the upregulation of the DNA sensor IFI16. IFI16 acts as a critical mediator linking DDR signaling to pathological ECM remodeling and fibrosis. Pharmacological inhibition of the upstream DDR pathway effectively mitigates IFI16 induction, attenuates cardiac fibrosis, and improves cardiac function. This study identifies the DDR-IFI16-ECM remodeling axis as a crucial contributor to DCM pathogenesis and highlights its potential as a therapeutic target for mitigating adverse cardiac remodeling and dysfunction.