Glucocorticoid-activated IRE1α/XBP-1s signaling: an autophagy-associated protective pathway against endotheliocyte damage

American Journal of Physiology. Cell Physiology
Yanchun GaoChangqing Zhang

Abstract

Glucocorticoid-induced endothelial injury has been reported in several diseases. Although there are several theories, the exact mechanism underlying the role of glucocorticoids in this process remains unclear. Autophagy has been reported to occur as a response to different stimuli and can affect cell survival and function. In this study, we found that glucocorticoids induced apoptosis and endoplasmic reticulum (ER) stress in endotheliocytes. Furthermore, we discovered that glucocorticoids induced autophagy in these cells and the inositol requiring protein 1 (IRE1α)/X-box binding protein 1s (XBP-1s) axis, one of the downstream signaling pathways of ER stress, was associated with the glucocorticoid-induced autophagy. The autophagy partly protected endotheliocytes from glucocorticoid-induced apoptosis and inhibition of proliferation. In conclusion, glucocorticoid-induced endoplasmic reticulum stress activated the IRE1α/XBP-1s signaling and induced autophagy, which, in turn, played a protective role in endotheliocyte survival and proliferation, avoiding further cellular damage caused by glucocorticoids.

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Citations

Jun 13, 2020·Frontiers in Oncology·Xin-Ying LiYuan-Gang Lu
May 1, 2021·International Journal of Molecular Sciences·Gustavo José da Silva PereiraClaudia Bincoletto
Dec 9, 2020·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Ya MaHuizhen Zhang

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Methods Mentioned

BETA
transfection
electrophoresis
FACS
flow cytometry
confocal microscopy
fluorescence microscopy
acetylation

Software Mentioned

SPSS
Quantity One

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