Gao Ruoyu, Tang Haiying, Mao Jingwei
Department of Gastroenterology, First Affiliated Hospital of Dalian Medical University, Dalian, 116011, People's Republic of China.
Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Dalian Medical University, Dalian, 116011, People's Republic of China.
J Inflamm Res. 2023 Sep 1;16:3897-3910. doi: 10.2147/JIR.S427868. eCollection 2023.
Programmed cell death (PCD) is a comprehensive term that encompasses various forms of cell death, such as apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy, which play a crucial role in the pathogenesis of liver fibrosis. PCD facilitates the elimination of aberrant cells, particularly activated hepatic stellate cells (HSCs), which are the primary producers of extracellular matrix (ECM). The removal of HSCs may impede ECM synthesis, thereby mitigating liver fibrosis. As such, PCD has emerged as a promising therapeutic target for the development of novel drugs to treat liver fibrosis. Numerous studies have been conducted to investigate the underlying mechanisms of PCD in the elimination of activated HSCs and other aberrant liver cells in fibrotic liver tissue, including hepatocytes, hepatic sinusoid endothelial cells (LSECs), and Kupffer cells (KCs). The induction of PCD, the interplay between different forms of PCD, and the potential harm or benefit of PCD in liver fibrosis are topics of ongoing research. Evidences suggest that PCD is a complex process with dual effects on liver fibrosis. The purpose of this review is to summarize the most recent advances in PCD and liver fibrosis research.
程序性细胞死亡（PCD）是一个综合性术语，涵盖了多种形式的细胞死亡，如凋亡、坏死性凋亡、焦亡、铁死亡和自噬，这些在肝纤维化的发病机制中起着关键作用。PCD有助于清除异常细胞，特别是活化的肝星状细胞（HSC），它们是细胞外基质（ECM）的主要产生者。清除HSC可能会阻碍ECM的合成，从而减轻肝纤维化。因此，PCD已成为开发治疗肝纤维化新药的一个有前景的治疗靶点。已经进行了大量研究来探究PCD在清除纤维化肝组织中活化的HSC和其他异常肝细胞（包括肝细胞、肝窦内皮细胞（LSEC）和库普弗细胞（KC））中的潜在机制。PCD的诱导、不同形式PCD之间的相互作用以及PCD在肝纤维化中的潜在危害或益处是正在进行研究的课题。有证据表明，PCD是一个对肝纤维化具有双重作用的复杂过程。本综述的目的是总结PCD和肝纤维化研究的最新进展。
