@article{oai:repo.qst.go.jp:00048152,
 author = {Hazawa, Masaharu and Yasuda, Takeshi and Saotome-Nakamura, Ai and Tomiyama, Kenichi and Chizuka, Obara and Goto, Takaya and Katsushi, Tajima and 羽澤 勝治 and 安田 武嗣 and 富山 健一 and 小原 千寿香 and 後藤 孝也 and 田嶋 克史},
 journal = {Vascular Pharmacology},
 month = {Dec},
 note = {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 (T381) and furin-resistant VN (A381). 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 (T381) 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.},
 pages = {150--158},
 title = {Intra- and extracellular plasminogen activator inhibitor-1 regulate effect of vitronectin against radiation-induced endothelial cell death},
 volume = {87},
 year = {2016}
}