Chen Ting, Zhang Huan, Shan Wenqi, Zhou Jinxue, You Yanwen
Department of human anatomy, Henan University of Chinese Medicine, Zhengzhou, 450046, Henan, China.
Department of Hepatobiliary and Pancreatic Surgery, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450003, Henan, China.
Biochem Biophys Res Commun. 2025 Jun 20;766:151881. doi: 10.1016/j.bbrc.2025.151881. Epub 2025 Apr 23.
Liver sinusoidal endothelial cells (LSECs) are highly specialized endothelial cells that form the interface between the hepatic vasculature and parenchymal cells, playing a crucial role in maintaining hepatic homeostasis. Under pathological conditions, LSECs undergo capillarization, marked by the loss of fenestrae and formation of a basement membrane, thereby impairing microcirculation and promoting fibrosis. Beyond capillarization, LSECs experience a spectrum of pathological changes-including angiogenesis, endothelial-to-mesenchymal transition (EndMT), autophagy, and senescence-all of which contribute to fibrogenesis through distinct molecular pathways. Moreover, LSECs orchestrate liver fibrotic remodeling through dynamic crosstalk with hepatic stellate cells (HSCs), hepatocytes, Kupffer cells, and immune cells, exerting both pro- and anti-fibrotic effects. This review comprehensively summarizes LSECs dysfunction in hepatic fibrosis, with a particular focus on intercellular communication and emerging therapeutic strategies. Elucidating the regulatory networks that govern LSECs behavior may uncover new opportunities for the diagnosis and treatment of chronic liver disease.
肝窦内皮细胞（LSECs）是高度特化的内皮细胞，形成肝血管系统与实质细胞之间的界面，在维持肝脏内环境稳态中发挥关键作用。在病理条件下，LSECs会发生毛细血管化，其特征是窗孔丧失和基底膜形成，从而损害微循环并促进纤维化。除了毛细血管化，LSECs还经历一系列病理变化，包括血管生成、内皮-间充质转化（EndMT）、自噬和衰老，所有这些都通过不同的分子途径促进纤维化。此外，LSECs通过与肝星状细胞（HSCs）、肝细胞、库普弗细胞和免疫细胞的动态相互作用来协调肝脏纤维化重塑，发挥促纤维化和抗纤维化作用。本综述全面总结了LSECs在肝纤维化中的功能障碍，特别关注细胞间通讯和新兴治疗策略。阐明调控LSECs行为的调控网络可能为慢性肝病的诊断和治疗带来新机遇。
