低氧诱导因子1α与低氧相关疾病信号通路的关系

Relationship between hypoxia inducible factor 1 alpha and hypoxia signaling pathway

背景:众所周知,PI3K/Akt/mTOR、MAPK、Jak/Stat、NF-κB、Notch等信号通路在细胞增殖分化、基因转录、免疫炎症介导等过程中扮演着重要角色,而低氧诱导因子1α作为低氧反应过程中的核心因子,在介导低氧信号通路中发挥着至关重要的作用。目的:总结了低氧诱导因子1α与低氧相关疾病信号通路的关系,以期为高原病的研究和治疗提供新思路。方法:应用计算机检索2000至2019年PubMed、Medline数据库,以及2011至2019年中国知网、万方数据库发表的相关文献,检索关键词为“hypoxia inducible factor 1α,signal pathway”“低氧诱导因子1α,信号通路”。结果与结论:在低氧相关疾病(炎症、肿瘤、心脑血管疾病)及高原病发生过程中,低氧诱导因子1α和相关信号通路中的关键因子的表达水平会发生不同程度变化。低氧诱导因子1α与低氧条件下所激活的信号通路关系密切,在经典的PHDs/HIF-1α/pVHL通路的基础上,调控这些信号通路的分子表达水平,或者受到这些信号通路的调控导致自身表达水平升高或降低,以应对低氧环境给机体带来的变化。

BACKGROUND:It is generally known that PI3K/Akt/mTOR,MAPK,Jak/Stat,NF-κB and Notch signaling pathways play important roles in cell proliferation and differentiation,gene transcription,and immune inflammation.Hypoxia inducible factor-1α(HIF-1α)plays a crucial role in mediating the hypoxia signaling pathway and acts as a core factor in the hypoxic reaction process.OBJECTIVE:To summarize the relationship between HIF-1αand hypoxia signaling pathways,providing new ideas for the research and treatment of altitude diseases.METHODS:English literatures published during 2000-2019 were retrieved from PubMed and Medline.Chinese literatures published during 2011-2019 were retrieved from CNKI and WanFang databases.Search terms were“hypoxia inducible factor 1α,signal pathway”in English and Chinese,respectively.RESULTS AND CONCLUSION:During the occurrence of hypoxic-related diseases(inflammation,tumor,cardiovascular and cerebrovascular diseases)and altitude disease,the expression levels of HIF-1 and the key factors of these signaling pathways can change to varying degrees.HIF-1 is closely related to these signaling pathway under the hypoxic conditions,regulates molecular expression in these signaling pathways,or are regulated by these signaling pathways to increase or decrease,in response to the changes in the body under hypoxia conditions.