TGF-β信号转导通路与遗传性脑小血管病

TGF-βsignal transduction pathway and hereditary cerebral small vessel diseases

转化生长因子-β(transforming growth factorβ,TGF-β)是一类具有生物活性的调节因子,广泛表达于内皮细胞、神经细胞、成纤维细胞、上皮细胞等。TGF-β可通过介导Smad依赖通路和非Smad依赖通路参与多种遗传性脑小血管病(cerebral small vessel disease,CSVD),如CADASIL、CARASIL、HTRA1基因突变相关CSVD(症状携带者)、Fabry病等的发生发展。TGF-β信号通路可能通过影响内皮细胞功能、血管壁结构改变、血脑屏障通透性增加等导致CSVD。但此通路的调节异常不能作为一元论来解释CSVD的发生。本文将对TGF-β蛋白家族及其受体,TGF-β信号转导通路及其转导机制,TGF-β信号通路与遗传性CSVD等方面进行综述。

Transforming growth factorβ(TGF-β)is a kind of biologically active regulatory factor,and is widely expressed in endothelial cells,nerve cells,fibroblasts,epithelial cells,etc.TGF-βcan participate in hereditary cerebral small vessel diseases(CSVD),such as CADASIL,CARASIL,and HTRA1 gene mutation-related CSVD(symptomatic carriers)and Fabry disease mediating Smad-dependent and-independent signaling pathways.The TGFβsignaling pathway may lead to CSVD by affecting endothelial cell function,structural changes in the vascular wall,and increased permeability of the blood-brain barrier.However,the dysregulation of this pathway cannot be used as a monism to explain the occurrence of CSVD.Therefore,TGFβprotein family and its receptors,TGF-βsignal transduction pathway and its transduction mechanism,and TGF-βsignal pathway and hereditary CSVD are reviewed in this article.