オクニシ　カツヒデ   Okunishi Katsuhide   奥西　勝秀    所属   東邦大学  医学部 医学科    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Inhibition of protein translation as a novel mechanism for prostaglandin E2 regulation of cell functions.
掲載誌名	正式名：FASEB journal : official publication of the Federation of American Societies for Experimental Biology ISSNコード：0892-6638/1530-6860
掲載区分	国外
出版社	FEDERATION AMER SOC EXP BIOL
巻・号・頁	28(1),pp.56-66
著者・共著者	Katsuhide Okunishi,Angela J DeGraaf,Zbigniew Zasłona,Marc Peters-Golden
発行年月	2014/01
概要	Prostaglandin E2 (PGE2) regulates numerous biological processes by modulating transcriptional activation, epigenetic control, proteolysis, and secretion of various proteins. Scar formation depends on fibroblast elaboration of matrix proteins such as collagen, and this process is strongly suppressed by PGE2 through activation of cAMP-dependent protein kinase A (PKA). However, the actual mechanism by which PGE2-PKA signaling inhibits collagen expression in fibroblasts has never been delineated, and that was the objective of this study. PGE2 unexpectedly induced a rapid reduction in procollagen I protein expression in adult lung fibroblasts, with a half-maximum effect at 1.5 h. This effect reflected its inhibition of translation rather than transcription. Global protein synthesis was also inhibited by PGE2. This action was mediated by PKA and involved both activation of ribosomal protein (rpS6) and suppression of mammalian target of rapamycin (mTOR). Similar effects of PGE2 were demonstrated in mouse peritoneal macrophages (PMs). These findings identify inhibition of translation as a new mechanism by which PGE2 regulates cellular function and a novel example of translational inhibition mediated by opposing actions on two distinct translational control pathways. Translational inhibition would be expected to contribute to dynamic alterations in cell function that accompany the changing PGE2 levels observed in disease states and with various pharmacotherapies.
DOI	10.1096/fj.13-231720
PMID	24072780