内皮联蛋白在血管生成中的调控机制及作用

Regulatory Mechanism and Function of Endoglin in Angiogenesis

机体新生血管的形成和稳态的维持是保证组织细胞正常生命活动的重要基础。参与血管生成这一生理过程的因子众多,血管生成机制复杂,该过程的异常与血管疾病、肿瘤和癌症的发生密切相关。内皮联蛋白(endoglin,ENG)是一种主要在内皮细胞上表达的I型跨膜糖蛋白,其作为转化生长因子β家族的辅助受体在调控血管生成与稳态中发挥着重要作用。随着基质金属蛋白酶14(matrix metalloproteinase 14,MMP14)、整合素、血管生成性糖蛋白LRG1(leucine-rich alpha-2-glycoprotein-1,LRG1)、G蛋白信号调节体-G alpha相互作用蛋白C端(GAIP interacting protein C-terminus,GIPC)等越来越多与ENG具有相互作用的蛋白质被鉴定出来,关于ENG调控血管生成的分子机制的研究已有了一定的进展,但各个蛋白质之间错综复杂的调控网络仍有待探究和梳理。阐明ENG及其互作的蛋白质的特征、对信号传导的影响和对血管生成的贡献,对于理解机体在生理、病理条件下如何精细、有序地调控血管生成至关重要,且对于相关疾病的临床治疗手段的研究具有重要意义。本文系统总结了ENG与TGF-β及非TGF-β家族相关蛋白质的互作及在调控血管生成中的作用,并对未来ENG相关研究方向做出展望,以期为研究ENG在相关血管疾病中的机制提供分子层面的指导。

The formation of new blood vessels and homeostasis are important to ensure the normal physiological activities of cells.The blood vessel formation is strictly regulated by many factors for the stabilities and functions of internal environment and immune systems.Endoglin(ENG),a type I transmembrane glycoprotein mainly expressed on endothelial cells,plays an important role in angiogenesis and homeostasis by acting as a co-receptor of transforming growth factorβfamily.With more and more proteins interacting with ENG have been uncovered,such as matrix metalloproteinase 14(MMP14),integrin,leucine-rich alpha-2-glycoprotein-1(LRG1)and GAIP interacting protein C-terminus(GIPC),many new research progresses in molecular mechanism of ENG have been developing recently.However,the exquisite regulatory network between these proteins remains to be explored and combed.Understanding the characteristics of these proteins,their influences in signal transduction and their contribution to angiogenesis under patho-physiological conditions will be helpful for the development of novel therapeutics.This review summarized the interactions between ENG and TGF-βor non-TGF-βfamily associated proteins in regulating angiogenesis.We also proposed some suggestions for future study on ENG allowing us to better understand the mechanisms of ENG-associated diseases.