A review published in
Genes & Diseases highlights the
prostaglandin E2 receptor subtype 4 (EP4) as an important regulator of inflammation and a promising therapeutic target for a wide range of inflammatory and inflammation-related diseases. By examining the diverse actions of the
PGE2–EP4 signaling pathway, the article demonstrates how targeting this receptor could provide more precise approaches to controlling inflammation.
Inflammation is a vital defense mechanism that helps the body respond to pathogens and harmful stimuli. However, excessive, insufficient or poorly regulated inflammatory responses can contribute to numerous diseases.
Prostaglandin E2 (PGE2) is a major lipid mediator involved in inflammation and acts through four receptor subtypes: EP1, EP2, EP3 and EP4. Among these,
EP4 is widely distributed throughout the body and participates in processes including inflammation, pain, blood pressure regulation, water and salt metabolism, tissue repair and tumor development.
EP4 can activate several important molecular pathways, including
cAMP–PKA, PI3K–AKT, NF-κB and β-arrestin signaling. This complex signaling network allows the receptor to produce different, and sometimes opposing, effects depending on the type of cell, stage of disease and surrounding biological environment.
The article describes the involvement of EP4 in conditions including
rheumatoid arthritis, osteoarthritis, inflammatory bowel disease, viral hepatitis, glomerulonephritis, myocarditis, atherosclerosis, inflammatory skin diseases, asthma and cancer. Its contrasting actions are particularly significant. Blocking EP4 may help reduce inflammation and joint damage in
rheumatoid arthritis, while activating the receptor may support intestinal mucosal repair in
inflammatory bowel disease.
In
asthma, EP4 activation may provide both anti-inflammatory and bronchodilatory benefits. Conversely, EP4 signaling can promote harmful immune responses in some inflammatory skin conditions. In
cancer, PGE2–EP4 signaling can contribute to an immunosuppressive tumor environment, potentially weakening the immune system’s ability to attack malignant cells. Several
EP4 antagonists have already progressed into clinical trials for solid tumors, including combinations with immunotherapies.
These contrasting effects underline the importance of
precision targeting. Conventional
non-steroidal anti-inflammatory drugs (NSAIDs) broadly reduce prostaglandin production and can produce unwanted effects in some conditions. Selectively activating or inhibiting EP4 could offer a more focused alternative. Understanding exactly when and where EP4 should be stimulated or blocked could ultimately support
safer, more targeted treatments for inflammatory diseases while opening new therapeutic possibilities across multiple areas of medicine.
# # # # # #
Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis is placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.
Scopus CiteScore: 10.4 |Impact Factor:14.6
# # # # # #
More information: https://www.keaipublishing.com/en/journals/genes-and-diseases/
Editorial Board: https://www.keaipublishing.com/en/journals/genes-and-diseases/editorial-board/
All issues and articles in press are available
online in
ScienceDirect (
https://www.sciencedirect.com/journal/genes-and-diseases).
Submissions to
Genes & Diseases may be made using
Editorial Manager (
https://www.editorialmanager.com/gendis/default.aspx).
Print ISSN: 2352-4820
eISSN: 2352-3042
CN: 50-1221/R
Contact Us: editor@genesndiseases.cn
X (formerly twitter): @GenesNDiseases (
https://x.com/GenesNDiseases)
# # # # # #
Reference
Shuxuan Li, Tong Wang, Anran Niu, Yuyan Du, Dong Zhou, Liang Gao, Haining Zhou, Shengnan Du, The update of prostaglandin E2 receptor subtype 4 (EP4) in inflammatory diseases, Genes & Diseases, Volume 13, Issue 6, 2026, 102169,
https://doi.org/10.1016/j.gendis.2026.102169
Funding
National Natural Science Foundation of China
81700638
Zhengzhou University College Students' innovation and entrepreneurship training program (Henan, China)
2024cxcy523
Zhengzhou University College Students' innovation and entrepreneurship training program (Henan, China)
2023CXCY371