Role of EP4 prostaglandin E2 receptor in the ischemic liver.
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.
Kuzumoto
Y
Y
Department of Surgery, Nara Medical University School of Medicine, Nara, Japan.
Sho
M
M
Ikeda
N
N
Mizuno
T
T
Hamada
K
K
Akashi
S
S
Tsurui
Y
Y
Kashizuka
H
H
Nomi
T
T
Kanehiro
H
H
Nakajima
Y
Y
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001483:Base Sequence; D017931:DNA Primers; D015232:Dinoprostone / Q000502:physiology*; D007249:Inflammation; D007511:Ischemia / Q000503:physiopathology*; D008102:Liver Circulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000235:genetics / Q000502:physiology*; D058309:Receptors, Prostaglandin E, EP4 Subtype; D015427:Reperfusion Injury / Q000503:physiopathology* / Q000517:prevention & control; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; C545651:Ptger4 protein, mouse; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D015232:Dinoprostone