Mo Hanjun, Yue Pengfei, Li Qiaoqi, Tan Yinxi, Yan Xinran, Liu Xinyue, Xu Yuanwei, Luo Yingzhe, Palihati Suruiya, Yi Cheng, Zhang Hua, Yuan Minlan, Yang Biao
Abdominal Oncology Ward, Division of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, No. 37 Guoxue Alley, Chengdu, 610041, Sichuan, China.
Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing, China.
Angiogenesis. 2025 Feb 3;28(2):14. doi: 10.1007/s10456-025-09969-5.
Liver sinusoidal endothelial cells (LSECs), with their unique morphology and function, have garnered increasing attention in chronic liver disease research. This review summarizes the critical roles of LSECs under physiological conditions and in two representative chronic liver diseases: metabolic dysfunction-associated steatotic liver disease (MASLD) and liver cancer. Under physiological conditions, LSECs act as selective barriers, regulating substance exchange and hepatic blood flow. Interestingly, LSECs exhibit contrasting roles at different stages of disease progression: in the early stages, they actively resist disease advancement and help restore sinusoidal homeostasis; whereas in later stages, they contribute to disease worsening. During this transition, LSECs undergo capillarization, lose their characteristic markers, and become dysfunctional. As the disease progresses, LSECs closely interact with hepatocytes, hepatic stellate cells, various immune cells, and tumor cells, driving processes such as steatosis, inflammation, fibrosis, angiogenesis, and carcinogenesis. Consequently, targeting LSECs represents a promising therapeutic strategy for chronic liver diseases. Relevant therapeutic targets and potential drugs are summarized in this review.
肝窦内皮细胞（LSECs）凭借其独特的形态和功能，在慢性肝病研究中受到越来越多的关注。本综述总结了LSECs在生理条件下以及在两种典型慢性肝病——代谢功能障碍相关脂肪性肝病（MASLD）和肝癌中的关键作用。在生理条件下，LSECs作为选择性屏障，调节物质交换和肝血流。有趣的是，LSECs在疾病进展的不同阶段表现出相反的作用：在早期，它们积极抵抗疾病进展并有助于恢复肝窦稳态；而在后期，它们则促使疾病恶化。在此转变过程中，LSECs发生毛细血管化，失去其特征性标志物并功能失调。随着疾病进展，LSECs与肝细胞、肝星状细胞、各种免疫细胞和肿瘤细胞密切相互作用，推动脂肪变性、炎症、纤维化、血管生成和致癌等过程。因此，靶向LSECs是慢性肝病一种有前景的治疗策略。本综述总结了相关治疗靶点和潜在药物。
