Department of Orthopedic Surgery, Shanghai Jiaotong University Affiliated Sixth People's Hospital , Shanghai , China.
Am J Physiol Cell Physiol. 2018 Sep 1;315(3):C300-C309. doi: 10.1152/ajpcell.00009.2018. Epub 2018 May 16.
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.
糖皮质激素诱导的内皮损伤已在多种疾病中报道。虽然有几种理论，但糖皮质激素在这一过程中作用的确切机制仍不清楚。自噬已被报道作为对不同刺激的反应，并且可以影响细胞存活和功能。在这项研究中，我们发现糖皮质激素诱导内皮细胞凋亡和内质网（ER）应激。此外，我们发现糖皮质激素诱导这些细胞中的自噬，并且内质网应激的下游信号通路之一，肌醇需求蛋白 1（IRE1α）/X 盒结合蛋白 1s（XBP-1s）轴与糖皮质激素诱导的自噬有关。自噬部分保护内皮细胞免受糖皮质激素诱导的凋亡和增殖抑制。总之，糖皮质激素诱导的内质网应激激活了 IRE1α/XBP-1s 信号通路，并诱导了自噬，自噬继而在内皮细胞存活和增殖中发挥保护作用，避免了糖皮质激素引起的进一步细胞损伤。
