Cardiomyocyte GSDME Drives Doxorubicin-Induced Cardiotoxicity by Targeting the CCL2-CCR2 Axis

作者：Junqiang Xue, Shiyao Xie, Xuelin Cheng, Enyong Su, Xiaoyue Song, Lili Wei, Yu Peng, Ming Liu, Hong Jiang · 发表于：International Journal of Biological Sciences · 年份：2025 · DOI：10.7150/ijbs.115489 · 被引用次数：7 · 研究领域：Synthesis and Biological Evaluation、Chemotherapy-induced cardiotoxicity and mitigation、Enzyme function and inhibition

knockout dampened DOX-induced cardiac CCL2-CCR2 signaling and inflammation, while CCL2 inhibition or CCR2+ macrophage depletion attenuated DIC. Mechanistically, GSDME facilitated mitochondrial injury in cardiomyocytes to release mtDNA and activated the STING/NFκB pathway, further targeting the CCL2-CCR2 axis and cardiac inflammation, thereby aggravating DIC. These findings identify GSDME as a potential therapeutic target for DIC.