Cdc42作为功能性因子调控纤维化

Cdc42 as A Functional Meditation Factor in Fibrosis

细胞分裂周期蛋白42(cell division control protein 42 homolog,Cdc42)是一种Rho蛋白家族的小GTPase,可与GTP或GDP结合并在其活性型或失活型之间的转换充当"分子开关",参与了细胞黏附、迁移与极化的过程。纤维化是引起器官功能丧失的重要原因之一,有许多不同的机制可以导致纤维化。以往的研究表明,Cdc42与癌症、心血管疾病、神经退行性病变等有密切的联系,却未提及Cdc42与纤维化之间存在的直接联系。该文总结最新的研究成果,讨论了Cdc42与肝、肾、肺以及心血管纤维化的关系。除此之外,该文也阐述了Cdc42通过细胞黏附迁移、上皮–间质转化等途径导致纤维化的具体机制,以及Cdc42介导的信号通路在纤维化过程中发挥的作用,同时还致力于研究各类关键因子之间的联系及与Rho蛋白质家族的"交谈(crosstalk)",更进一步完善了纤维化发生机制,并提出针对Cdc42的靶向治疗方式,以拓宽纤维化的治疗方案。

Cell division control protein 42 homolog（Cdc42） is a small G protein of Rho family, acting as a ＂molecular switch＂, cycling between an active GTP-bound and an inactive GDP-bound, and involving in cell adhesion, migration and polarization process. Fibrosis is an important cause of the organ function losing. Previous studies indicated that Cdc42 has a close relationship with cancer, cardiovascular diseases, neurodegenerative diseases without mentioning the direct relationship between Cdc42 and fibrosis. This review combines the most advanced research results with previous investigation to discuss liver fibrosis, renal interstitial fibrosis, pulmonary fibrosis and cardiovascular fibrosis that meditated by Cdc42. It also describes the Cdc42-induced mechanism in fibrosis like cell adhesion and migration and epithelial-mesenchymal transition（EMT）.Cdc42-mediated signaling pathways involving in the process of fibrosis,their association with various key factors and＂crosstalk＂with other Rho GTPases are also discussed.More importantly,the specific therapies for Cdc42 are discussed in order to complete the pathogenesis of fibrosis and broaden the treatment of fibrosis.