TITLE

Prostaglandin E2 receptor EP4 agonist induces Bcl-xL and independently activates proliferation signals in mouse primary hepatocytes

AUTHOR(S)
Kataoka, Kojiro; Takikawa, Yasuhiro; De Lin, Shi; Suzuki, Kazuyuki
PUB. DATE
June 2005
SOURCE
Journal of Gastroenterology;Jun2005, Vol. 40 Issue 6, p610
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background. To improve the survival rate of fulminant hepatic failure (FHF), we examined the mechanism of the antiapoptotic effect, and the possible proliferative effect, of a specific agonist of prostaglandin E2 receptor EP4 (PGEP4-A) on mouse primary hepatocytes, as a candidate for a new therapeutic agent. Methods. The expression of four PGE2 receptor subtypes was detected by a reverse transcriptase polymerase chain reaction (PCR) method. Hepatocytes were stimulated with PGEP4-A, ONO-AE1-437, and changes in the expression levels of Bcl-xL and cyclin D1 and in the phosphorylation of epidermal growth factor receptor (EGF-R) and extracellular-signal related kinase (ERK) were examined by Western blot analysis. Results. Mouse primary hepatocytes constitutively expressed the mRNAs of all four PGE2 receptor subtypes, including that of PGEP4. PGEP4-A induced not only Bcl-xL protein expression (as we had previously demonstrated in HepG2 cells) but also induced cyclin D1 protein expression in mouse primary hepatocytes as well as the phosphorylation of EGF-R and ERK. The inhibition of ERK phosphorylation by a specific inhibitor, PD98059, did not affect the increase in Bcl-xL expression level. Conclusions. PGEP4-A may be a therapeutic agent for FHF because of its antiapoptotic and regenerative effects on hepatocytes.
ACCESSION #
17577076

 

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