Liver sinusoidal endothelial cells (LSECs) are liver-specific endothelial cells with the highest permeability than other mammalian endothelial cells, characterized by the presence of fenestrae on their surface, the absence of diaphragms and lack of basement membrane. Located at the interface between blood and other liver cell types, LSECs mediate the exchange of substances between the blood and the Disse space, playing a crucial role in maintaining substance circulation and homeostasis of multicellular communication. As the initial responders to chronic liver injury, the abnormal activation of LSECs not only changes their own physicochemical properties but also interrupts their communication with HSCs and hepatocytes, which collectively aggravates the process of liver fibrosis. In this review, we have comprehensively updated the various pathways by which LSECs were involved in the initiation and progression of liver fibrosis, including but not limited to cellular phenotypic change, the induction of capillarization, decreased permeability and regulation of intercellular communications. Additionally, the intervention effects and latest regulatory mechanisms of anti-fibrotic drugs involved in each aspect have been summarized and discussed systematically. As we studied deeper into unraveling the intricate role of LSECs in the pathophysiology of liver fibrosis, we unveil a promising horizon that pave the way for enhanced patient outcomes.

中文翻译：

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肝窦内皮细胞：肝纤维化中一个重要但经常被忽视的参与者。

肝窦内皮细胞（LSEC）是肝脏特异性内皮细胞，其通透性高于其他哺乳动物内皮细胞，其特点是表面有窗孔、无隔膜、无基底膜。LSEC 位于血液和其他肝细胞类型之间的界面，介导血液和 Disse 空间之间的物质交换，在维持物质循环和多细胞通讯的稳态中发挥着至关重要的作用。作为慢性肝损伤的最初反应者，LSECs的异常激活不仅改变了其自身的理化性质，而且中断了其与HSCs和肝细胞的通讯，从而共同加剧了肝纤维化的进程。在这篇综述中，我们全面更新了LSEC参与肝纤维化起始和进展的各种途径，包括但不限于细胞表型改变、毛细血管化的诱导、通透性降低和细胞间通讯的调节。此外，还对各个方面涉及的抗纤维化药物的干预效果和最新调控机制进行了系统的总结和讨论。随着我们深入研究 LSEC 在肝纤维化病理生理学中的复杂作用，我们揭示了一个充满希望的前景，为改善患者预后铺平了道路。