Activation of cGAS-STING signaling pathway promotes liver fibrosis and hepatic sinusoidal microthrombosis

• DOI: 10.1016/j.intimp.2023.111132
• Publication Date: 2023-11-09T20:00:17Z
• Authors: Shaobin Luo; Rongkun Luo; Huanyuan Lu; Rui Zhang; Gang Deng; Hongwu Luo; Xiao Yu; Changfa Wang; Hui Zhang; Yuping Zhang; Wei Huang; Jichun Sun; Yinghong Liu; Feizhou Huang; Zhao Lei
• Keywords: Proinflammatory cytokine; Hepatic fibrosis

Inflammation plays an essential role in the development liver fibrosis.The Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) is a central cytoplasmic DNA sensor which can recognize DNA, known to trigger stimulator of interferon genes (STING) and downstream proinflammatory factors. Here, we investigated cGAS-STING signaling pathway pathogenesis fibrosis.Differentially expressed (DEGs) human tissue were identified using RNA-Seq analysis. As models fibrosis, chronic Carbon tetrachloride (CCl4) exposure applied cGAS-knockout mice. LX-2 cells co-cultured with sinusoidal endothelial (LSECs) explore underlying mechanisms hepatic microthrombosis inflammatory microenvironment. The endoscopic ultrasound-guided portal vein pressure gradient (EUS-PPG) method was used analyze associations between PPG patients fibrosis hypertension (PTH). RNA-seq analysis results showed that DEGs enriched inflammation cell activation. upregulation exacerbated intrahepatic inflammation. It also LSECs impairment increased contribution vivo vitro. Prothrombotic mediators factors associated hypertension. Therefore, activating promotes microthrombosis, may lead pressure.