Aggravation of acute kidney injury by mPGES-2 down regulation is associated with autophagy inhibition and enhanced apoptosis.
Aggravation of acute kidney injury by mPGES-2 down regulation is associated with autophagy inhibition and enhanced apoptosis.
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mPGES-2 下调加重急性肾损伤与自噬抑制和细胞凋亡增强相关
DOI：
10.1038/s41598-017-10271-8
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发表时间：
2017-08-31
影响因子：
4.6
通讯作者：
Xiao X
中科院分区：
文献类型：
--
作者：
Li T;Liu Y;Zhao J;Miao S;Xu Y;Liu K;Liu M;Wang G;Xiao X
微粒体前列腺素E合成酶-2(mPGES-2)的缺失对活体PGE2的合成没有影响，目前该酶的功能尚不清楚。本研究探讨mPGES-2在内毒素诱导的大鼠急性肾损伤(AKI)中的表达及其在体内的作用。我们发现在脂多糖诱导的急性肾损伤小鼠肾脏中mPGES-2表达上调。抑制小鼠mpges2基因表达加剧了内毒素诱导的肾功能障碍、肾小管细胞损伤和细胞凋亡，同时抑制了肾脏自噬。进一步的细胞实验表明，mPGES-2过表达导致肾小管上皮细胞自噬增加，凋亡率降低。此外，自噬抑制剂3-甲基腺嘌呤可逆转上述结果。相反，siRNA干扰mPGES-2的表达降低了肾小管上皮细胞的自噬水平，但显著增加了肾小管上皮细胞的凋亡，而自噬诱导剂雷帕霉素可以逆转这一结果。总之，我们的研究表明，mPGES-2可以通过调节自噬水平来保护肾小管上皮细胞，下调mPGES-2对急性肾损伤的加重与抑制自噬和促进细胞凋亡有关。
The deletion of microsomal prostaglandin E synthase-2 (mPGES-2) does not affectin vivoPGE2production, 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) bothin vitroandin 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 over-expression 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.
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自噬限制内毒素急性肾损伤，并改变肾小管上皮细胞因子表达。
影响因子：
3.7
作者：
Leventhal JS;Ni J;Osmond M;Lee K;Gusella GL;Salem F;Ross MJ
通讯作者：
Ross MJ
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19.6
作者：
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4.8
作者：
Petiot, A;Ogier-Denis, E;Codogno, P
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Codogno, P
影响因子：
16
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Kroemer G;Mariño G;Levine B
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Levine B
影响因子：
2.9
作者：
Jania LA;Chandrasekharan S;Backlund MG;Foley NA;Snouwaert J;Wang IM;Clark P;Audoly LP;Koller BH
通讯作者：
Koller BH