Activation of Cyclooxygenase-2 by ATF4 During Endoplasmic Reticulum Stress Regulates Kidney Podocyte Autophagy Induced by Lupus Nephritis

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Juan JinQiang He

Abstract

Autophagy plays an essential role in lupus nephritis (LN)-induced kidney injury, although the mechanism of action remains obscure. We investigated the role of cyclooxygenase-2 (COX-2) and the ATF4 endoplasmic reticulum (ER) stress pathway in LN-induced podocyte autophagy. We evaluated podocyte autophagy in a mouse model of LN. Protein levels of COX-2 and ATF4, and markers of autophagy, were evaluated by immunofluorescence and western blotting. To evaluate apoptosis, levels of PGE2 were measured by enzyme-linked immunosorbent assay. LN induced kidney damage and dysfunction, which was associated with podocyte autophagy. COX-2 and the ATF4 ER stress pathway were induced by LN in cultured podocytes. Inhibition of COX-2 inhibited LN-induced autophagy in podocytes. In addition, blocking ER stress with 4-phenylbutyrate or RNAi partially counteracted COX-2 overexpression and LN-induced autophagy, suggesting that ER stress is required for LN-induced kidney autophagy. Furthermore, LN activated ATF4 and induced its nuclear translocation. Knockdown of ATF4 inhibited LN-induced COX-2 overexpression. Our study suggests a novel molecular mechanism by which COX2 overexpression, induced by the ATF4 ER stress pathway, contributes to LN-induced k...Continue Reading

Citations

Apr 7, 2020·American Journal of Physiology. Renal Physiology·Li XiangGuoshuang Xu
Aug 20, 2019·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·Wen-Qun ZhongJi-Hong Zhao
Feb 22, 2021·Archives of Medical Research·Jianzhang ZhengHong Wu
Mar 7, 2021·International Journal of Molecular Sciences·Chuang Li, Ying Maggie Chen
Jun 10, 2021·The International Journal of Neuroscience·Qi ChenXiaoyi Wang
Jul 2, 2021·Scientific Reports·Joaquín Miguel PellegriniVerónica Edith García
Jul 31, 2021·Biological Trace Element Research·Kangping LiuJianzhu Liu

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