The Glucocorticoid Induced Endoplasmic Reticulum Stress And Cell Apoptosis In Endothelial Cells

To investigate whether the endoplasmic reticulum(ER)stress is triggered in the glucocorticoid(GC)-induced endotheliocyte(EC)apoptosis and osteonecrosis of femoral head(ONFH),and whether inhibition of GC-induced ER stress is effective in the prevention of ONFH.To make it clear whether glucocorticoid induced endoplasmic reticulum stress can induce autophagy,we want to know the relationship between autophagy,apoptosis and proliferation induced by GC.The EC apoptosis was exacerbated by the DEXtreatment in a timeand concentration-dependent manner.The expression levels of the ER stress related proteins increased after DEX treatment.The inhibition of PERK significantly decreased the GC-induced EC apoptosis.The in vivo results indicated that a PERK inhibitor GSK2656157 protected the vascular injury and significantly prevented GC-induced ONFH.It is the first time that glucocorticoid induced autophagy has been demonstrated for the first time,and the IRE1α-XBP-1s pathway plays an important role in it.Overexpression of XBP-1s can effectively inhibit the apoptosis of PERK induced endothelial cells.ER stress was closely involved in GC-induced EC apoptosis and ONFH.PERK signaling,one of the three ER stress sensors,contributes to GC-induced ONFH and inhibition of PERK signaling is a potential target as a preventive strategy for treating GC-induced ONFH.IRE1α-XBP-1s signaling pathway can not only induce autophagy,but also inhibit autophagy,partially inhibit glucocorticoid induced apoptosis,and protect the endothelial cells from apoptosis.