美国伊利诺斯大学医学院Asrar B. Malik、Jalees Rehman等研究人员合作发现，线粒体DNA激活cGAS信号并抑制YAP介导的内皮细胞增殖程序，从而促进炎性损伤。2020年3月11日，《免疫》杂志在线发表了这一成果。
Title: mtDNA Activates cGAS Signaling and Suppresses the YAP-Mediated Endothelial Cell Proliferation Program to Promote Inflammatory Injury
Author: Long Shuang Huang, Zhigang Hong, Wei Wu, Shiqin Xiong, Ming Zhong, Xiaopei Gao, Jalees Rehman, Asrar B. Malik
Abstract: Cytosolic DNA acts as a universal danger-associated molecular pattern (DAMP) signal;however, the mechanisms of self-DNA release into the cytosol and its role in inflammatorytissue injury are not well understood. We found that the internalized bacterial endotoxinlipopolysaccharide (LPS) activated the pore-forming protein Gasdermin D, which formedmitochondrial pores and induced mitochondrial DNA (mtDNA) release into the cytosolof endothelial cells. mtDNA was recognized by the DNA sensor cGAS and generated thesecond messenger cGAMP, which suppressed endothelial cell proliferation by downregulatingYAP1 signaling. This indicated that the surviving endothelial cells in the penumbriumof the inflammatory injury were compromised in their regenerative capacity. In anexperimental model of inflammatory lung injury, deletion of cGas in mice restored endothelial regeneration. The results suggest that targeting theendothelial Gasdermin D activated cGAS-YAP signaling pathway could serve as a potentialstrategy for restoring endothelial function after inflammatory injury.