Pharmacologic Blockade of 15-PGDH Protects Against Acute Renal Injury Induced by LPS in Mice
发布时间：2021-06-02
点击次数：
影响因子：3.367
发表刊物：Front Physiol
关键字：AKI, 15-PGDH, LPS, autophagy, apoptosis, oxidative stress
摘要：Prostaglandin pathway plays multiple roles in various physiological and pathological conditions. The present study aimed to investigate the effect of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a key enzyme in the degradation of prostaglandins, on lipopolysaccharide (LPS)-induced acute kidney injury (AKI) in mice. In this study, male C57BL/6J mice were injected intraperitoneally with LPS (10 mg/kg). SW033291, a potent small-molecule inhibitor of 15-PGDH, was used to investigate the therapeutic potential of 15-PGDH inhibition on LPS-induced AKI. We discovered that the expression of 15-PGDH protein was upregulated in kidneys of LPS-stimulated mice, and it was mainly localized in the cytoplasm of renal tubular epithelial cells in renal cortex and outer medulla. SW033291 administration improved the survival rates of mice and attenuated renal injury of mice that were challenged by LPS. Additionally, inhibition of 15-PGDH also reversed LPS-induced apoptosis of renal cells, increased expression of anti-apoptotic protein Bcl-2, and downregulated expression of Fas, caspase-3, and caspase-8. Pretreatment of SW033291 enhanced autophagy in kidney cells after LPS stimulation. Our data also showed that inhibition of 15-PGDH relieved the level of lipid peroxidation and downregulated NADPH oxidase subunits induced by LPS in mice kidneys but had no significant effect on the release of inflammatory factors, such as IL-6, IL-1β, TNF-α, and MCP-1. Our study demonstrated that inhibition of 15-PGDH could alleviate LPS-induced AKI by regulating the apoptosis, autophagy, and oxidative stress rather than inflammation in mice.
合写作者：Jie Zhao,Ting Li,Chunjiang Wang,Yunfei Xu,Xiaoli Wang,Xianzhong Xiao
第一作者：Shuying Miao,Caihong Lv
论文类型：基础研究
通讯作者：Ying Liu,Huali Zhang(通讯作者)
学科门类：医学
一级学科：基础医学
期号：2020, 11:138.
是否译文：否
发表时间：2020-03-13
收录刊物：SCI