Hypoxia Affects Autophagy in Human Umbilical Vein Endothelial Cells via the IRE1 Unfolded Protein Response

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.

IRE1; JNK; autophagy; endoplasmic reticulum stress; hypoxia; unfolded protein response.