转化生长因子β/Smad信号通路在HIV致病机制中的作用

Progress on the roles of TGF-β/Smad signaling pathway in HIV pathogenesis

转化生长因子β(transforming growth factorβ,TGF-β)/Smad信号通路具有广泛的生物学活性,在调节细胞生长、粘附、分化、细胞动态平衡、免疫应答等方面起重要作用。该信号通路活性过高可促使疤痕形成、器官纤维化、免疫抑制和晚期癌症进展,而活性过低可导致炎症、发育异常、愈合不良和肿瘤发生。TGF-β/Smad信号通路的作用复杂,在不同情况下可表现为抑制或增强免疫、抑制或增强炎症的作用,但以抑制免疫和抑制炎症为主。在人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染过程中,TGF-β/Smad信号通路与HIV存在复杂的相互作用,HIV蛋白tat和gp120可诱导TGF-β表达;同时,该通路也可能对HIV感染和复制、潜伏病毒库、机体的免疫功能缺陷、HIV相关炎症产生影响。值得注意的是,主要表现为抗炎作用的TGF-β虽然被HIV所诱导,但较高的TGF-β似乎未能抑制HIV相关炎症。迄今有关TGF-β/Smad信号通路与HIV感染进展的相关性尚未清楚,它在HIV感染及相关疾病中的作用及机制还需进一步探讨和验证。本综述对TGF-β/Smad信号通路与HIV感染的相关研究进展进行总结,为更全面了解HIV的致病机制以及探讨艾滋病治疗的新思路提供参考。

TGF-β/Smad signaling pathway has a wide range of biological activities and plays an important roles in regulating cell growth,adhesion,differentiation,cell dynamic balance,and immune responses.The higher activity of TGF-β/Smad signaling pathway may promote scar formation,organ fibrosis,immunosuppression,and late-stage cancer progression,while low activity may lead to inflammation,dysplasia,poor healing and oncogenesis.The function of the TGF-β/Smad signaling pathway is extremely complex and can exhibit inhibitory or enhancing effects on immunity and inflammation under different circumstances,but immunosuppressive and anti-inflammatory effects are dominant.During HIV infection,the TGFβ/Smad signaling pathway interacts with HIV in a complex manner as HIV proteins tat and gp120 can induce TGF-βexpression.Meanwhile,this signaling pathway may also play a role in HIV infection and replication,latent virus reservoir,host immune deficiency and HIV-related inflammation.It is worth noting that even though TGF-β,which mainly exhibits antiinflammatory effects,is induced by HIV,high levels of TGF-βdo not seem to inhibit HIV-related inflammation.So far,the relationship between TGF-β/Smad signaling pathway and HIV infection has not been elucidated,and its role and mechanism in HIV infection and related illnesses need further exploration and validation.This review summarizes the relevant research progress on the TGF-β/Smad signaling pathway and HIV infection,and provides a reference for further understanding of HIV pathogenesis and exploring strategies of AIDS treatment.