外泌体介导低氧相关信号通路在疾病发生发展中的重要作用

Important role of exosomes-mediated hypoxia-related signaling pathways in the occurrence and progression of diseases

背景:目前,外泌体在低氧相关疾病及肿瘤疾病中作为疾病诊断的新生物标记物已取得瞩目的研究成果,成为预防和治疗低氧相关疾病的潜力选手。目的:从分子水平出发,综述外泌体干扰低氧相关信号通路改变低氧相关疾病发生发展过程的机制,为低氧相关疾病的研究和治疗提供依据。方法:以"hypoxia,exosomes,signal pathway"为英文检索词,以"低氧、外泌体、信号通路"为中文检索词,应用计算机检索2016年1月至2021年5月年PubMed、Medline、中国知网和万方数据库发表的相关文献,最终纳入文献56篇进行归纳分析。结果与结论:(1)低氧环境下,外泌体与一些低氧相关信号通路密切相关且互相调控,外泌体介导的低氧信号通路可能参与调控低氧相关疾病和肿瘤的发病过程。(2)外泌体经供体细胞释放,携带其信息由受体细胞接受,通过低氧诱导因子、磷脂酰肌醇三激酶/丝氨酸/苏氨酸激酶(PI3K/Akt)、核转录因子κB及转化生长因子β等与低氧相关的信号通路,介导疾病中的免疫应答、细胞增殖、迁移、血管生成及肿瘤侵袭等重要生理病理过程。(3)在低氧相关炎症疾病中,外泌体可诱导上述各低氧信号通路的激活,以减轻炎症损伤。(4)但在肿瘤疾病中,外泌体虽然诱导了上述各低氧信号通路激活,却促进肿瘤部位的血管生成,促进肿瘤细胞的侵袭和转移,使肿瘤进展加速,而这种作用可能与外泌体的细胞供体来源有关,但其具体调控机制仍需未来研究进一步明确。

BACKGROUND:At present,exosomes have made remarkable progress as new biomarkers for disease diagnosis in hypoxia-related diseases and tumor diseases,and have become potential players in the prevention and treatment of hypoxia-related diseases.OBJECTIVE:To explore the mechanism of exosomes interference with hypoxia-related signaling pathways to change the occurrence and development of hypoxia-related diseases at the molecular level,so as to provide a basis for the research and treatment of hypoxia-related diseases.METHODS:Using the search terms of"hypoxia,exosomes,signal pathway"in Chinese and English,articles published from January 2016 to May 2021 were retrieved from PubMed,Medline,CNKI,and Wanfang databases.Finally,56 articles were included for analysis.RESULTS AND CONCLUSION:(1)In hypoxic environment,exosomes are closely related to some hypoxia-related signaling pathways.Exosomes-mediated hypoxia signaling pathways may be involved in altering the pathogenesis of hypoxia-related diseases and tumor.(2)Through hypoxia inducible factor,phosphatidylinositol 3-kinase/serine/threonine kinase,nuclear factor κB,transforming growth factor β and other hypoxia-related signaling pathways,exosomes released by donor cells,carrying their information and accepted by recipient cells,mediate important physiological and pathological processes,such as immune response,cell proliferation,migration,angiogenesis,and tumor invasion in diseases.(3)In hypoxia-related inflammatory diseases,exosomes can induce the activation of the above-mentioned hypoxia signaling pathways to reduce inflammatory damage.(4)However,in tumor diseases,exosomes mediate the activation of above hypoxia-related signaling pathways,which accelerate the angiogenesis of tumor sites and promote the invasion and metastasis of tumor cells,resulting in the progression of tumor.This effect may be associated with the cell origin of exosomes.Further exploration is needed to understand its specific regulatory mechanism.