缺氧通过 IRE1 未折叠蛋白反应影响人脐静脉内皮细胞自噬。
Hypoxia Affects Autophagy in Human Umbilical Vein Endothelial Cells via the IRE1 Unfolded Protein Response.
机构信息
Department of Cardiology, Wuhan University Zhongnan Hospital, Wuhan, 430072, China.
School of Basic Medical Sciences, Wuhan University, Wuhan, 430072, China.
出版信息
Curr Med Sci. 2023 Aug;43(4):689-695. doi: 10.1007/s11596-023-2749-y. Epub 2023 Aug 10.
OBJECTIVE
The purpose of this study was to investigate the role of the unfolded protein response, specifically the inositol-requiring enzyme 1 (IRE1) signaling pathway, in hypoxia-induced autophagy in human umbilical venous endothelial cells (HUVECs).
METHODS
The expression of IRE1 and autophagy relative protein in HUVECs with hypoxia was explored by Western blotting, qRT-PCR and confocal microscopy. Further, we evaluated the biological effects of HUVECs by tube formation assay and wound healing assay in vitro. Finally, we examined the function of IRE1 in local blood vessels through animal models.
RESULTS
Hypoxia activated the IRE1 signaling pathway and induced autophagy in a time-dependent manner in HUVECs and further influenced the biological effects of HUVECs. Intraperitoneal injection of IRE1 inhibitors inhibited local vascular autophagy levels and lipid accumulation in model animals.
CONCLUSION
Hypoxia can induce autophagy and activate the IRE1 signaling pathway in HUVECs and the IRE1 signaling pathway is involved in autophagy in hypoxic conditions.
目的
本研究旨在探讨未折叠蛋白反应（UPR），特别是肌醇需求酶 1（IRE1）信号通路，在人脐静脉内皮细胞（HUVEC）缺氧诱导自噬中的作用。
方法
通过 Western blot、qRT-PCR 和共聚焦显微镜研究缺氧状态下 HUVEC 中 IRE1 和自噬相关蛋白的表达。进一步通过体外管形成实验和划痕愈合实验评估 HUVEC 的生物学效应。最后，通过动物模型研究 IRE1 在局部血管中的作用。
结果
缺氧以时间依赖性方式激活 HUVEC 中的 IRE1 信号通路并诱导自噬，进一步影响 HUVEC 的生物学效应。腹腔注射 IRE1 抑制剂可抑制模型动物局部血管自噬水平和脂质堆积。
结论
缺氧可诱导 HUVEC 自噬并激活 IRE1 信号通路，IRE1 信号通路参与缺氧状态下的自噬。
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