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	Plasmin overcomes resistance to prostaglandin E2 in fibrotic lung fibroblasts by reorganizing protein kinase A signaling.
掲載誌名	正式名：The Journal of biological chemistry ISSNコード：0021-9258
掲載区分	国外
出版社	AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
巻・号・頁	286(37),pp.32231-43
著者・共著者	Katsuhide Okunishi,Thomas H Sisson,Steven K Huang,Cory M Hogaboam,Richard H Simon,Marc Peters-Golden
発行年月	2011/09/16
概要	Collagen deposition by fibroblasts contributes to scarring in fibrotic diseases. Activation of protein kinase A (PKA) by cAMP represents a pivotal brake on fibroblast activation, and the lipid mediator prostaglandin E(2) (PGE(2)) exerts its well known anti-fibrotic actions through cAMP signaling. However, fibrotic fibroblasts from the lungs of patients with idiopathic pulmonary fibrosis, or of mice with bleomycin-induced fibrosis, are resistant to the normal collagen-inhibiting action of PGE(2). In this study, we demonstrate that plasminogen activation to plasmin restores PGE(2) sensitivity in fibrotic lung fibroblasts from human and mouse. This involves amplified PKA signaling resulting from the promotion of new interactions between AKAP9 and PKA regulatory subunit II in the perinuclear region as well as from the inhibition of protein phosphatase 2A. This is the first report to show that an extracellular mediator can dramatically reorganize and amplify the intracellular PKA-A-kinase anchoring protein signaling network and suggests a new strategy to control collagen deposition by fibrotic fibroblasts.
DOI	10.1074/jbc.M111.235606
PMID	21795691