| First Author | Yao L | Year | 2016 |
| Journal | Am J Physiol Gastrointest Liver Physiol | Volume | 310 |
| Issue | 11 | Pages | G1071-80 |
| PubMed ID | 27102561 | Mgi Jnum | J:235167 |
| Mgi Id | MGI:5793008 | Doi | 10.1152/ajpgi.00327.2015 |
| Citation | Yao L, et al. (2016) Microsomal prostaglandin E synthase-1 protects against Fas-induced liver injury. Am J Physiol Gastrointest Liver Physiol 310(11):G1071-80 |
| abstractText | Microsomal prostaglandin E synthase-1 (mPGES-1) is the terminal enzyme for the synthesis of prostaglandin E2 (PGE2), a proproliferative and antiapoptotic lipid molecule important for tissue regeneration and injury repair. In this study, we developed transgenic (Tg) mice with targeted expression of mPGES-1 in the liver to assess Fas-induced hepatocyte apoptosis and acute liver injury. Compared with wild-type (WT) mice, the mPGES-1 Tg mice showed less liver hemorrhage, lower serum alanine transaminase (ALT) and aspartate transaminase (AST) levels, less hepatic necrosis/apoptosis, and lower level of caspase cascade activation after intraperitoneal injection of the anti-Fas antibody Jo2. Western blotting analysis revealed increased expression and activation of the serine/threonine kinase Akt and associated antiapoptotic molecules in the liver tissues of Jo2-treated mPGES-1 Tg mice. Pretreatment with the mPGES-1 inhibitor (MF63) or the Akt inhibitor (Akt inhibitor V) restored the susceptibility of the mPGES-1 Tg mice to Fas-induced liver injury. Our findings provide novel evidence that mPGES-1 prevents Fas-induced liver injury through activation of Akt and related signaling and suggest that induction of mPGES-1 or treatment with PGE2 may represent important therapeutic strategy for the prevention and treatment of Fas-associated liver injuries. |
