Roles of Lysophosphatidic Acid in Various Fibrotic Diseases

2012 Fiscal Year Final Research Report

• Project/Area Number: 23790071
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Tohoku University
• Principal Investigator: OKUDAIRA Shinichi 東北大学, 大学院・薬学研究科, 助教 (90570060)
• Project Period (FY): 2011 – 2012
• Keywords: リゾホスファチジン酸 / オートタキシン / 線維症

Research Abstract

Lysophosphatdic acid (LPA) has recently been implicated in various fibrotic disease, including pulmonary fibrosis, renal fibrosis and peritoneal fibrosis. It is, however, not clear in which way LPA is produced and how LPA production is regulated in these fibrotic diseases. In this study, by studying expression of LPA-producing enzyme, autotaxin (ATX), and quantifying substrate of ATX using LC/MS, we found that LPA infibrotic diseases is regulated by up-regulation of both ATX and its substrate, lysophosphatidylcholine (LPC).

Research Products

• [Journal Article] Constitutivelymphocyte transmigration across the basal lamina of high endothelial venules is regulated by the autotaxin/lysophosphatidic acid axis (2013)
  • Author(s): Bai Z, Cai L, Umemoto E, Takeda A, Tohya K, Komai Y, Veeraveedu PT, Hata E, Sugiura Y, Kubo A, Suematsu M, Hayasaka H, Okudaira S, Aoki J, Tanaka T, Albers HM, Ovaa H, Miyasaka M
  • Journal Title: J Immunol Volume: 190(5)巻 Pages: 2036-2048
  • DOI: DOI:10.4049/jimmunol.1202025.
  • Peer Reviewed
• [Journal Article] Identification and biochemical characterization of a novel autotaxin isoform, ATXδ, with a four-amino acid deletion (2012)
  • Author(s): Hashimoto T, Okudaira S, Igarashi K, Hama K, Yatomi Y, Aoki J
  • Journal Title: J Biochem Volume: 151(1)巻 Pages: 89-97
  • DOI: DOI:10.1093/jb/mvr126.
  • Peer Reviewed
• [Journal Article] Autotaxin regulates vascular development via multiple lysophosphatidic acid (LPA) receptors in zebrafish (2011)
  • Author(s): Yukiura H, Hama K, Nakanaga K, Tanaka M, Asaoka Y, Okudaira S, Arima N, Inoue A, Hashimoto T, Arai H, Kawahara A, Nishina H, Aoki J
  • Journal Title: J Biol Chem Volume: 286(51)巻 Pages: 43972-43983
  • DOI: DOI:10.1074/jbc.M111.301093.
  • Peer Reviewed
• [Journal Article] Serum autotaxin measurements in pregnant women: application for the differentiation of normal pregnancy and pregnancy-induced hypertension (2011)
  • Author(s): Masuda A, Fujii T, Iwasawa Y, Nakamura K, Ohkawa R, Igarashi K, Okudaira S, Ikeda H, Kozuma S, Aoki J, Yatomi Y
  • Journal Title: Clin Chim Acta Volume: 412(21-22)巻 Pages: 1944-1950
  • DOI: DOI:10.1016/j.cca.2011.06.039.
  • Peer Reviewed
• [Journal Article] Autotaxin regulates vascular development via multiple lysophosphatidic acid (LPA) receptorsFluorescence probe forlysophospholipase C/NPP6 activity and a potent NPP6 inhibitor (2011)
  • Author(s): Yukiura H, Hama K, Nakanaga K, Tanaka M, Asaoka Y, Okudaira S, Arima N, Inoue A, Hashimoto T, Arai H, Kawahara A, Nishina H, Aoki J
  • Journal Title: J Am Chem Soc Volume: 133(31)巻 Pages: 12021-12030
  • DOI: DOI:10.1021/ja201028t.
  • Peer Reviewed
• [Presentation] 線維症におけるリゾホスファチジン酸の解析 (2013)
  • Author(s): 奥平真一、久保裕司、青木淳賢
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-28
• [Presentation] リゾホスファチジン酸産生酵素オートタキシンの結晶構造解析 (2011)
  • Author(s): 奥平真一、西増弘志、濱弘太郎、三原恵美子、堂前直、井上飛鳥、石谷隆一郎、高木淳一、濡木理、青木淳賢
  • Organizer: 第53回日本脂質生化学会
  • Place of Presentation: 仙台
  • Year and Date: 2011-07-23
• [Presentation] リゾホスファチジン酸産生酵素オートタキシンの結晶構造解析 (2011)
  • Author(s): 奥平真一、西増弘志、濱弘太郎、三原恵美子、堂前直、井上飛鳥、石谷隆一郎、高木淳一、濡木理、青木淳賢
  • Organizer: 第53回日本脂質生化学会
  • Place of Presentation: 東京
  • Year and Date: 2011-05-11