Ptger4, the prostaglandin E2 receptor 4, is crucial in maintaining gut homeostasis. It is involved in the prostaglandin E2 (PGE2) signaling pathway, where PGE2 produced by mesenchymal stromal cells can stimulate Ptger4 in epithelial cells [2]. Ptger4 has significance in immune regulation, bone metabolism, and is associated with various diseases [4]. Genetic models, especially knockout mouse models, have been pivotal in understanding its functions.

In a Csf1r-iCre Ptger4fl/fl mouse model of DSS-induced colitis, the absence of Ptger4 in macrophages led to defective mucosal healing and epithelial barrier regeneration. Mechanistically, PGE2 triggers CXCL1 secretion in monocyte-derived PTGER4+ macrophages via mitogen-activated protein kinases (MAPKs), and CXCL1 drives epithelial cell differentiation and proliferation during colitis [1]. In the context of intestinal tumorigenesis, epithelial-specific ablation of Ptger4 in mutant mice misdirected the regenerative reprogramming of stem cells, preventing Sca-1+ cell expansion and sporadic tumour initiation, demonstrating the role of PGE2-Ptger4 in controlling tumour-initiating stem cells [3].

In conclusion, Ptger4 plays essential roles in maintaining the integrity of the intestinal epithelium and in the regulation of intestinal tumorigenesis as revealed through gene-knockout mouse models. These findings highlight its potential as a therapeutic target, especially in diseases like inflammatory bowel disease and colorectal cancer.