Aggravation of acute kidney injury by mPGES-2 down regulation is associated with autophagy inhibition and enhanced apoptosis

作者：Li, Ting; Liu, Ying^*; Zhao, Jie; Miao, Shuying; Xu, Yunfei; Liu, Ke; Liu, Meidong; Wang, Guiliang; Xiao, Xianzhong^*

来源：Scientific Reports, 2017, 7(1): 10247.

DOI：10.1038/s41598-017-10271-8

• ISCHEMIA-REPERFUSION INJURY
• PROSTAGLANDIN-E SYNTHASE
• ACUTE-RENAL-FAILURE
• IN-VITRO
• MACROAUTOPHAGY
• PROTEIN
• SEPSIS
• DEGRADATION
• INFLAMMATION
• INDUCTION

The deletion of microsomal prostaglandin E synthase-2 (mPGES-2) does not affect in vivo PGE(2) production, and the function of this enzyme remains unknown until now. This study investigated the expression and roles of mPGES-2 in LPS induced acute kidney injury (AKI) both in vitro and in vivo. We found that mPGES-2 was up-regulated in kidney of mice with LPS induced AKI. Inhibition of mouse mpges2 gene expression exacerbated LPS-induced renal dysfunction, renal tubular cell damage and apoptosis, while inhibited kidney autophagy. Further cellular experiments showed that overexpression of mPGES-2 resulted in increased autophagy and decreased apoptosis rate of renal tubular epithelial cells. In addition, treatment with autophagy inhibitor 3-methyladenine could reverse the above-mentioned results. On the contrary, interference of mPGES-2 expression by siRNA decreased autophagy level but significantly increased apoptosis of tubular epithelial cells and treatment with autophagy inducer rapamycin can reverse these results. Overall, our study shows that mPGES-2 can protect renal tubular epithelial cells by regulating autophagy levels and aggravation of acute kidney injury by mPGES-2 down regulation is associated with autophagy inhibition and enhanced apoptosis.

• 出版日期2017-8-31
• 单位长治医学院; 中南大学; 赣南医学院