Ptger4, the prostaglandin E2 receptor 4, is crucial for maintaining homeostasis in the gut. It is involved in signaling pathways related to inflammation resolution, mucosal healing, and cell differentiation. The PGE2-Ptger4 signaling axis has been shown to be significant in various biological processes [1,2,3].

In a Csf1r-iCre Ptger4fl/fl mouse model, conditional knockout of Ptger4 in macrophages led to defective mucosal healing and epithelial barrier regeneration during dextran sulfate sodium (DSS)-induced colitis. Mechanistically, PGE2 triggers CXCL1 secretion in monocyte-derived PTGER4+ macrophages via MAPKs, which drives epithelial cell differentiation and proliferation. Targeting macrophages with liposomes loaded with an MAPK agonist restored defective epithelial regeneration in these mice [1]. In another study, 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 paracrine control of tumour-initiating stem cells by PGE2-Ptger4 [3].

In conclusion, Ptger4 is essential for processes such as mucosal healing, epithelial barrier regeneration, and regulation of stem-cell function in the gut. Studies using Ptger4 knockout and conditional knockout mouse models have revealed its role in intestinal inflammation, tumour initiation, and potentially other disease conditions, highlighting its potential as a therapeutic target, especially in inflammatory bowel disease and colorectal cancer [1,3].

References:

1. Na, Yi Rang, Jung, Daun, Stakenborg, Michelle, Matteoli, Gianluca, Seok, Seung Hyeok. 2021. Prostaglandin E2 receptor PTGER4-expressing macrophages promote intestinal epithelial barrier regeneration upon inflammation. In Gut, 70, 2249-2260. doi:10.1136/gutjnl-2020-322146. https://pubmed.ncbi.nlm.nih.gov/33558271/

2. Anbazhagan, Murugadas, Sharma, Garima, Murthy, Shanta, Kugathasan, Subra, Matthews, Jason D. 2024. PTGER4 signaling regulates class IIa HDAC function and SPINK4 mRNA levels in rectal epithelial cells. In Cell communication and signaling : CCS, 22, 493. doi:10.1186/s12964-024-01879-1. https://pubmed.ncbi.nlm.nih.gov/39396982/

3. Roulis, Manolis, Kaklamanos, Aimilios, Schernthanner, Marina, Kollias, George, Flavell, Richard A. 2020. Paracrine orchestration of intestinal tumorigenesis by a mesenchymal niche. In Nature, 580, 524-529. doi:10.1038/s41586-020-2166-3. https://pubmed.ncbi.nlm.nih.gov/32322056/