Inflammasomes and Pyroptosis of Liver Cells in Liver Fibrosis.

Inflammasomes and Pyroptosis of Liver Cells in Liver Fibrosis.
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肝纤维化中的炎症小体和肝细胞焦亡

DOI:
10.3389/fimmu.2022.896473
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发表时间:
2022
影响因子:
7.3
通讯作者:
--
中科院分区:
医学2区
文献类型:
--
作者:

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炎性小体是一种多蛋白复合物,可以感知危险信号并激活caspase-1介导促炎细胞因子释放和细胞死亡。有两种主要的经典和非经典信号通路触发炎性小体激活。炎症体在肝中响应于肝损伤而在实质和非实质细胞中表达和组装。此外,肝细胞、胆管上皮细胞(胆管细胞)、肝星状细胞(HSC)、肝巨噬细胞和肝窦内皮细胞(LSEC)通过不同的机制促进肝纤维化。然而,肝纤维化中这些肝细胞中的炎性小体和焦亡的潜在机制仍然是难以捉摸的。本文综述了炎性小体复合物的激活和功能,并讨论了炎性小体、肝细胞凋亡和肝纤维化之间的关系。与其他类似的评论者不同,我们将重点关注在肝纤维化发展过程中各种肝细胞中炎性小体激活和焦亡的影响。我们还将重点介绍炎性小体介导的肝纤维化的药物干预的最新进展。
Inflammasomes are multiprotein complexes that can sense danger signals and activate caspase-1 to mediate pro-inflammatory cytokines release and pyroptotic cell death. There are two main canonical and non-canonical signaling pathways that trigger inflammasome activation. Inflammasomes are expressed and assembled in parenchymal and nonparenchymal cells in response to liver injury in the liver. Additionally, the hepatocytes, biliary epithelial cells (cholangiocytes), hepatic stellate cells (HSCs), hepatic macrophages, and liver sinusoidal endothelial cells (LSECs) contribute to liver fibrosis via different mechanisms. However, the underlying mechanism of the inflammasome and pyroptosis in these liver cells in liver fibrosis remains elusive. This review summarizes the activation and function of inflammasome complexes and then discusses the association between inflammasomes, pyroptosis, and liver fibrosis. Unlike other similar reviewers, we will focus on the effect of inflammasome activation and pyroptosis in the various liver cells during the development of liver fibrosis. We will also highlight the latest progress of pharmacological intervention in inflammasome-mediated liver fibrosis.
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