Ptges2-KO Mouse

Ptges2, also known as microsomal prostaglandin E synthase-2 (mPGES-2), is a key enzyme in the synthesis of prostaglandin E2 (PGE2) from COX-derived PGH2 [3]. It is involved in multiple biological pathways, such as the arachidonic acid metabolism pathway [4]. PGE2, the product of Ptges2-catalyzed reaction, has a wide range of biological activities and is involved in inflammation, fever, and other physiological processes. Genetic models, like gene knockout mice, have been crucial in studying Ptges2's function.

In mouse models, global or tubule-specific knockout of Ptges2 led to decreased renal dysfunction and morphological damage induced by cisplatin and unilateral renal ischemia/reperfusion, suggesting that blocking Ptges2 may be a promising therapeutic strategy for acute kidney injury (AKI) as it inhibits ferroptosis via the heme-dependent regulation of the p53/SLC7A11/GPX4 axis [1]. Also, global knockout or pharmacological blockage of Ptges2 in mice attenuated diabetic podocyte injury and tubulointerstitial fibrosis, alleviating lipid accumulation and lipotoxicity in diabetic kidney disease (DKD), as mPGES-2 and Rev-Erbα compete for heme binding to regulate fatty acid binding protein 5 expression and lipid metabolism in the diabetic kidney [2].

In conclusion, Ptges2 is essential for PGE2 synthesis and is involved in important biological processes. The study of Ptges2 using KO mouse models has revealed its significance in diseases like AKI and DKD, providing potential therapeutic directions for these conditions.

References:

1. Zhong, Dandan, Quan, Lingling, Hao, Chang, Jia, Zhanjun, Sun, Ying. 2023. Targeting mPGES-2 to protect against acute kidney injury via inhibition of ferroptosis dependent on p53. In Cell death & disease, 14, 710. doi:10.1038/s41419-023-06236-7. https://pubmed.ncbi.nlm.nih.gov/37907523/

2. Zhong, Dandan, Chen, Jingshuo, Qiao, Ranran, Jia, Zhanjun, Sun, Ying. 2024. Genetic or pharmacologic blockade of mPGES-2 attenuates renal lipotoxicity and diabetic kidney disease by targeting Rev-Erbα/FABP5 signaling. In Cell reports, 43, 114075. doi:10.1016/j.celrep.2024.114075. https://pubmed.ncbi.nlm.nih.gov/38583151/

3. Nakatani, Yoshihito, Kudo, Ichiro. . [Prostaglandin E2 synthases]. In Nihon yakurigaku zasshi. Folia pharmacologica Japonica, 120, 373-8. doi:. https://pubmed.ncbi.nlm.nih.gov/12528468/

4. Zhao, Zhibo, Liu, Xinyi, Xiang, Yue, Gong, Jianping, Zhao, Lei. 2023. Inhibiting cholesterol de novo synthesis promotes hepatocellular carcinoma progression by upregulating prostaglandin E synthase 2-mediated arachidonic acid metabolism under high fatty acid conditions. In Cancer science, 115, 477-489. doi:10.1111/cas.16035. https://pubmed.ncbi.nlm.nih.gov/38081591/