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

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

[Laser inducing mucosal fibrosis for preventing recurrence of esophageal varices].

OBJECTIVE: To investigate the prevention of esophageal varices recurrence by laser inducing esophageal mucosal fibrosis. METHODS: Our study included 42 patients after esophageal varices eradicated by endoscopic varices ligation, and they were divided into 2 groups randomly, each group included 21 patients. One group was assigned to received laser treatment, and indocyanine green solution (1 mg/ml) was injected submucosally, a diode laser (power 10 watts) was applied to the surface from the esophagogastric junction to 5 cm above it. Another group was controlling without any treatments. All patient were followed up by endoscopy every 3 months until 12 months. RESULTS: Laser irradiation was performed safely without any major complications. And lower esophageal mucosa produced fibrosis widely after laser irradiated 1 month. After 12 months follow up, the cumulative recurrence rate was significantly lower than the control group, 14% (3/21) vs 43% (9/21) (chi(2) = 4.20, P < 0.05). CONCLUSIONS: Our study indicates that laser inducing mucous fibrosis is safely and can prevent recurrence of esophageal varices.