オバラ　チズカ   Obara Chizuka   小原　千寿香    所属   東邦大学  理学部 生物学科    職種   博士研究員
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Intra- and extracellular plasminogen activator inhibitor-1 regulate effect of vitronectin against radiation-induced endothelial cell death
掲載誌名	正式名：VASCULAR PHARMACOLOGY ISSNコード：1537-1891/1879-3649
出版社	ELSEVIER SCIENCE INC
巻・号・頁	87,pp.150-158
著者・共著者	Masaharu Hazawa,Takeshi Yasuda,Ai Saotome-Nakamura,Kenichi Tomiyama,Chizuka Obara,Takaya Goto,Katsushi Tajima
発行年月	2016/12
概要	Plasminogen activator inhibitor-1 (PAI-1) is induced by radiation resulting in endothelial cell impairment, potentially leading to multiple organ failure. Vitronectin (VN) is a 75-kDa glycoprotein (VN75) cleaved into two forms (VN75 or VN65/10) by furin, which is regulated by intracellular PAI-1. VN protects against radiation-induced endothelial cell death, but the mechanisms involved in VN processing and its interactions with intra- and extracellular PAI-1 remain unclear. We examined these processes in cells in vitro using recombinant proteins or overexpression of VN and PAI-1 genes, including furin-susceptible (T-381) and furin-resistant VN (A(381)). VN processing was analyzed using a mutant PAI-1 with relatively weaker binding to VN. VN function was evaluated by survival of radiation-damaged endothelial cells. Wild-type, but not mutant PAI-1 inhibited furin-dependent VN processing. Gene transfer revealed that furin-susceptible VN was processed more than the furin-resistant form, but processing of both was inhibited by PAI-1 overexpression. Intracellular PAI-1 formed a complex with VN75 (T-381) in cells and media, and the VN75 form was secreted preferentially. Only VN75 protected against radiation-induced endothelial cell death, in which its effect was abolished by wild-type but not mutant PAI-1. These findings indicate that intracellular PAI-1 inhibits VN processing and protects against radiation-induced endothelial cell death. (C) 2016 Elsevier Inc. All rights reserved.
DOI	10.1016/j.vph.2016.09.006
PMID	27650166