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

Yanchun Gao1, Hongyi Zhu1, Fan Yang1

  • 1Department of Orthopedic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital , Shanghai , China.

Insights

Glucocorticoids cause endoplasmic reticulum stress and autophagy in endotheliocytes. This autophagy, activated by the IRE1α/XBP-1s pathway, protects cells from glucocorticoid-induced damage and apoptosis.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Pathology

Background:

  • Glucocorticoid-induced endothelial injury is a recognized phenomenon in various diseases.
  • The precise molecular mechanisms linking glucocorticoids to endothelial dysfunction remain incompletely understood.
  • Autophagy is a cellular process involved in stress response and cell survival.

Purpose of the Study:

  • To elucidate the role of autophagy in glucocorticoid-induced endotheliocyte injury.
  • To investigate the signaling pathways involved in glucocorticoid-induced autophagy.
  • To determine the functional consequences of autophagy in endotheliocytes under glucocorticoid exposure.

Main Methods:

  • Treatment of endotheliocytes with glucocorticoids.
  • Assessment of apoptosis and endoplasmic reticulum (ER) stress.
  • Analysis of autophagy induction and the involvement of the IRE1α/XBP-1s pathway.
  • Evaluation of cell proliferation and survival.

Main Results:

  • Glucocorticoids induced apoptosis and ER stress in endotheliocytes.
  • Glucocorticoids stimulated autophagy, which was linked to the IRE1α/XBP-1s signaling pathway.
  • Autophagy partially protected endotheliocytes from glucocorticoid-induced apoptosis and proliferation inhibition.

Conclusions:

  • Glucocorticoid-induced ER stress activates the IRE1α/XBP-1s pathway, leading to autophagy.
  • Autophagy plays a protective role in endotheliocyte survival and proliferation against glucocorticoid-induced damage.

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