Rho蛋白与肝星状细胞

Rho proteins and hepatic stellate cells

小G蛋白Rho家族是一类能结合GTP的蛋白质,在细胞信号传导通路中发挥着"分子开关"的作用,能通过下游蛋白产生多种生物学效应.肌动蛋白细胞骨架是维持细胞形态,介导真核细胞必需的生物学功能的重要结构,参与细胞收缩、迁移和生存等多个过程.肝星状细胞(hepatic stellate cells,HSCs)是肝纤维化形成过程和调节门脉血流的关键细胞,其肌动蛋白细胞骨架的变化反映了HSCs的活化状态.故本文重点介绍Rho家族在对HSCs的肌动蛋白细胞骨架重构、细胞收缩、迁移及生存方面的调控机制,进而探讨对Rho家族及其信号途径的调控是否能成为抗门脉高压和肝纤维化治疗的新靶点.

The Rho family small GTPases can act as molecular switches in eukaryotic signal transduction and exert diverse biological effects through a variety of downstream effector proteins. The actin cytoskeleton is important in maintaining cell shape, mediating many important biological functions in eukaryotic cells and controlling cell contraction, movement and survival. Hepatic stellate cells （HSCs） activation plays a key role in the formation of liver fibrosis and the regulation of portal blood flow. Rho proteins can direct activation-associated changes in HSC morphology via regulation of the actin cytoskeleton. In this article, we will review the mechanisms underlying the roles of Rho family small GTPases in regulating actin cytoskeleton remodeling and cell contractility, movement and survival in HSC cells. Furthermore, we explore the possibility that the Rho family small GTPase- associated signal pathway is used as a new target for treating hepatic fibrosis and portal hypertension.