依赖于微环境的TGFβ信号

转化生长因子β（transforming growth factor β,TGFβ）家族成员是一类分泌的细胞因子,在胚胎发育、免疫调节、伤口修复、细胞增殖和抑制等过程中发挥重要作用。其中,TGFβ1、TGFβ2和TGFβ3在进化上最晚出现,并以潜伏态分泌。有别于家族中的大多数成员,TGFβ1-3的信号具有时空区域性,并依赖于其所处的微环境。阐明依赖于微环境的TGFβ信号的多层次调控机制对于理解TGFβ信号在免疫、癌症等生理、病理条件下的功能,以及开发临床治疗策略具有重要意义。本文从TGFβ前体复合物的结构入手,并从TGFβ的激活,配体-受体识别,跨膜信号传导及转录调控等方面,论述依赖于微环境的TGFβ信号的调控机制,同时讨论肿瘤微环境中多效的TGFβ信号,进而对今后的研究方向进行展望。

Microenvironment-dependent TGFβ Signaling

Members of transforming growth factor beta (TGFβ) family are secreted cytokines that play important roles in embryonic development, immune regulation, wound healing, and cell proliferation and inhibition. Compared with other family members, TGFβ subfamily members, including TGFβ1, TGFβ2 and TGFβ3, evolved later in development. Unlike others of the family, TGFβ1-3 are secreted in latent configuration and spatial-temporally regulated in a manner depending on their microenvironments. Understanding the multi-level regulation of TGFβ signaling under patho-physiological conditions in immunity and cancer biology will be helpful for the development of novel therapeutic strategies. Herein, we reviewed the literatures on the studies of TGFβ signaling. Especially, we introduced the structural studies of TGFβ1 pro-complex and dissected the regulatory of TGFβ signaling from the perspectives of TGFβ activation, ligand-receptor recognition, transmembrane signaling and transcriptional regulation. Moreover, we discussed pleiotropic signaling of TGFβ in tumor microenvironment and provided our perspectives for future studies in this field.