Ptges2, also known as microsomal prostaglandin E synthase-2 (mPGES-2), is an enzyme involved in the synthesis of prostaglandin E2 (PGE2) from COX-derived PGH2 [4]. It is part of the arachidonic acid metabolism pathway and is of great biological importance in regulating various physiological and pathological processes [5]. Genetic models, such as KO/CKO mouse models, are valuable tools for studying its functions.

In AKI models, both global and tubule-specific mPGES-2-deficient mice treated with cisplatin or subjected to unilateral renal ischemia/reperfusion showed decreased renal dysfunction and morphological damage, indicating that mPGES-2 blockage may be a promising therapeutic strategy, likely through inhibiting ferroptosis via the heme-dependent regulation of the p53/SLC7A11/GPX4 axis [2]. In DKD models, global knockout or pharmacological blockage of mPGES-2 attenuated diabetic podocyte injury and tubulointerstitial fibrosis, ameliorating lipid accumulation and lipotoxicity, with mPGES-2 and Rev-Erbα competing for heme binding to regulate fatty acid binding protein 5 expression and lipid metabolism in the diabetic kidney [3]. In the context of brown fat, METTL14-mediated m6A promotes the decay of Ptges2, and BAT-specific knockdown of Ptges2 reverses the insulin-sensitizing effects in M14KO mice, revealing a role of Ptges2 in regulating systemic insulin sensitivity [1].

In conclusion, Ptges2 is crucial in the synthesis of PGE2 and participates in multiple biological processes. Studies using KO/CKO mouse models have revealed its significant roles in diseases like AKI, DKD, and in regulating systemic insulin sensitivity. These findings provide potential therapeutic targets for these disease areas.