消皮素D在肝脏疾病病理进展中的作用

Role of gasdermin D in the pathological progression of liver diseases

消皮素D(GSDMD)在免疫炎症反应效能放大及细胞焦亡过程中扮演重要角色。其被caspase-1切割活化后,GSDMD-N端快速释放,锚定在细胞膜上并形成孔隙,随即引发细胞焦亡,同时伴随强促炎因子IL-1β和IL-18大量释放。急/慢性肝脏炎症反应、细胞死亡是病毒性肝炎、酒精性肝病、非酒精性脂肪性肝病、自身免疫性肝病、肝衰竭及肝细胞癌等肝脏疾病的共有病理特征。本文在概述GSDMD基本结构特点后,详细分析了其在多种肝脏疾病病理进展所扮演的重要角色。此外,提出了针对GSDMD为潜在治疗靶点的防治策略,可为肝脏疾病临床防治下一步研究的重点方向提供新的思路。

As a novel star molecule,gasdermin D(GSDMD)plays an important role in the amplification of immune inflammatory response and the process of pyroptosis.After being cleaved and activated by caspase-1,the N-terminal of GSDMD is rapidly released,which anchors on the cell membrane and forms pores,thereby leading to pyroptosis,accompanied by the release of a large amount of the strong proinflammatory factors IL-1βand IL-18.Acute/chronic liver inflammatory response and cell death are the common pathological features of liver diseases such as viral hepatitis,alcoholic liver disease,nonalcoholic fatty liver disease,autoimmune liver disease,liver failure,and hepatocellular carcinoma.This article summarizes the basic structural characteristics of GSDMD and elaborates on its important role in the pathological progression of various liver diseases.In addition,it is proposed that prevention and treatment strategies with GSDMD as a potential therapeutic target can provide new ideas for further studies on the clinical prevention and treatment of liver diseases.