Ptges, known as prostaglandin E synthase, is a key enzyme in the arachidonic acid pathway responsible for the synthesis of prostaglandin E2 (PGE2). PGE2 is involved in multiple biological processes such as inflammation, cell growth, and immune response [1-6, 8-10]. Dysregulation of the Ptges-PGE2 axis has been associated with various diseases, highlighting its biological importance. Genetic models, like gene knockout mouse models, can be valuable for studying its functions.

In lung fibrosis, Ptges is upregulated and contributes to myofibroblast differentiation via the HIF-1α-dependent glycolysis pathway [1]. In colorectal cancer, depletion of Ptges enhances the sensitivity of cancer cells to 5-fluorouracil, as Ptges/PGE2 axis modulates glycolysis in these cells [2]. In Gprc5a-knockout mice, Ptges/PGE2 signaling is highly associated with lung tumorigenesis and metastasis mainly through immunosuppression [3]. In pancreatic ductal adenocarcinoma, higher Ptges expression is observed, correlated with metabolic and immune reprogramming [4]. In non-small cell lung cancer, dysregulated Ptges promoted tumor migration and metastasis, and knockdown of Ptges suppressed these features [5]. In osteosarcoma, FUBP1 confers lobaplatin resistance by transcriptionally activating Ptges and facilitating the arachidonic acid metabolic pathway [6].

In conclusion, Ptges, through the production of PGE2, is involved in critical biological processes related to fibrosis, cancer development, and drug resistance. The use of gene knockout models in mice has significantly contributed to understanding its role in these disease areas, providing insights into potential therapeutic targets for treating lung fibrosis, colorectal cancer, lung cancer, pancreatic cancer, and osteosarcoma.