Role of EP4 prostaglandin E2 receptor in the ischemic liver.

Abstract

Prostaglandin E(2) (PGE(2)) mediates a variety of both innate and adaptive immunity responses through 4 distinct receptors, EP1-4. Recent studies have suggested the physiological and pathological role of EP4 in various inflammatory diseases. In this study, we investigated the importance of the EP4 receptor, and the efficacy of a selective EP4 agonist to alter hepatic ischemia/reperfusion (I/R) injury, an important cause of damage in liver resection and transplantation. We used an established murine I/R injury model, 70% partial hepatic ischemia for 90 minutes in male C57BL/6 mice. The local expression of EP4 messenger RNA (mRNA) in the naive and the ischemic liver at 2 hours after reperfusion was examined using RT-PCR analysis. Some mice received the EP4 selective agonist during I/R. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured as markers of hepatic injury. EP4 expression in the liver was significantly up-regulated at 2 hours after reperfusion. Furthermore, treatment with EP4 agonist significantly inhibited hepatic injury at 6 hours after reperfusion. Our data suggest an inhibitory role of EP4 PGE(2) receptor in hepatic I/R injury and the therapeutic efficacy of a selective EP4 agonist for liver protection.

• Authors: Y Kuzumoto, M Sho, N Ikeda, T Mizuno, K Hamada, S Akashi, Y Tsurui, H Kashizuka, T Nomi, H Kanehiro, Y Nakajima
• Journal: Transplantation proceedings (Transplant Proc) 2005 Jan-Feb Vol. 37 Issue 1 Pg. 422-4 ISSN: 0041-1345 [Print] United States
• PMID: 15808664 (Publication Type: Journal Article)

Chemical References

• DNA Primers
• Ptger4 protein, mouse
• RNA, Messenger
• Receptors, Prostaglandin E
• Receptors, Prostaglandin E, EP4 Subtype
• Aspartate Aminotransferases
• Alanine Transaminase
• Dinoprostone

Topics

• Alanine Transaminase (blood)
• Animals
• Aspartate Aminotransferases (blood)
• Base Sequence
• DNA Primers
• Dinoprostone (physiology)
• Inflammation
• Ischemia (physiopathology)
• Liver Circulation
• Male
• Mice
• Mice, Inbred C57BL
• RNA, Messenger (genetics)
• Receptors, Prostaglandin E (agonists, genetics, physiology)
• Receptors, Prostaglandin E, EP4 Subtype
• Reperfusion Injury (physiopathology, prevention & control)
• Reverse Transcriptase Polymerase Chain Reaction