Regulation of proteolysis on epithelial cell membrane and its implication in the epithelial disorders

2010 Fiscal Year Self-evaluation Report

• Project/Area Number: 20390114
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: University of Miyazaki
• Principal Investigator: KATAOKA Hiroaki University of Miyazaki, 医学部, 教授 (10214321)
• Project Period (FY): 2008 – 2011
• Keywords: 分子 / プロテアーゼ

Research Abstract

細胞周囲微小環境におけるプロテアーゼ活性は、細胞外基質の再構成や生理活性物質の活性調節を介して、多細胞生物の様々な生命現象に深く関与する。本研究では、上皮細胞に特異的に発現する細胞膜結合型インヒビター(HAI-1 : HGF activator inhibitor type 1)とその標的プロテアーゼ(HGF activator, matriptaseなど)による上皮細胞周囲微小環境での生理活性物質プロセッシング制御と、その破綻によって生じる上皮組織の病態を解析する。特に(1) HGF activatorの新規基質の探索、(2) HAI-1 knockout (KO)マウスおよび組織特異的conditional KOマウスの作成とそれらを用いた諸臓器上皮組織における解析、(3)上皮系がんの進展におけるHAI-1の意義解析の3点に重点をおいて研究を行う。

Research Products

• [Journal Article] Hepatocyte growth factor activator inhibitor type 1 suppresses metastatic pulmonary colonization of pancreatic carcinoma cells. (2011)
  • Author(s): Fukushima T, Kawaguchi M, Yamasaki M, Tanaka H, Yorita K, Kataoka H
  • Journal Title: Cancer Sci 102 Pages: 407-413
  • Peer Reviewed
• [Journal Article] Hepatocyte growth factor activator (HGFA): pathophysiological functions in vivo. (2010)
  • Author(s): Kataoka H, Kawaguchi M
  • Journal Title: FEBS J. 277 Pages: 2230-2237
  • Peer Reviewed
• [Journal Article] Hepatocyte growth factor activator inhibitor type 1 regulates the epithelial to mesenchymal transition through membrane-bound serine proteinases. (2009)
  • Author(s): Cheng H, Fukushima T, Takahashi N, Tanaka H, Kataoka H
  • Journal Title: Cancer Res 69 Pages: 1828-1835
  • Peer Reviewed
• [Journal Article] Hepatocyte growth factor activator is a serum activator of single-chain precursor macrophage-stimulating protein. (2009)
  • Author(s): Kawaguchi M, Orikawa H, Baba T, Fukushima T, Kataoka H
  • Journal Title: FEBS J. 276 Pages: 3481-3490
  • Peer Reviewed
• [Journal Article] Defect of hepatocyte growth factor activator inhibitor type 1/serine protease inhibitor, Kunitz type 1 (Hai-1/Spint1) leads to ichthyosis-like condition and abnormal hair development in mice. (2008)
  • Author(s): Nagaike K, Kawaguchi M, Takeda N, Fukushima T, Sawaguchi A, Kohama K, Setoyama M, Kataoka H
  • Journal Title: Am.J.Pathol 173 Pages: 1464-1475
  • Peer Reviewed
• [Presentation] Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is required for the integrity of intestinal epithelium. (2010)
  • Author(s): Kawaguchi M, Fukushima T, Takeda N, Hoshiko S, Yorita K, Kohama K, Orikawa H, Baba T, Kataoka H
  • Organizer: Experimental Biology 2010
  • Place of Presentation: Anaheim CA, USA.
  • Year and Date: 2010-04-26
• [Presentation] Roles of HAI-1 in epithelial integrity and invasion of carcinoma cells. (2010)
  • Author(s): Kataoka H
  • Organizer: Gordon Research Conference on Plasminogen Activation & Extracellular Proteolysis
  • Place of Presentation: Ventura CA, USA.
  • Year and Date: 2010-02-17
• [Presentation] HAI-1 による上皮組織形態と上皮完全性の制御 (2009)
  • Author(s): 片岡寛章
  • Organizer: 第82回日本生化学会大会(シンポジウム)
  • Place of Presentation: 神戸
  • Year and Date: 2009-10-24
• [Presentation] Hepatocyte growth factor activator inhibitor type 1 regulates the epithelial to mesenchymal transition. (2009)
  • Author(s): Cheng H, Fukushima T, Takahashi N, Tanaka H, Kataoka H
  • Organizer: 100th Annual Meeting of the American Association for Cancer Research.
  • Place of Presentation: Denver, CO, USA.
  • Year and Date: 2009-04-19
• [Presentation] Hepatocyte growth factor activator is a serum activator of single-chain precursor of macrophage-stimulating protein. (2008)
  • Author(s): Kawaguchi M, Nagai M, Fukushima T, Orikawa H, Cheng H, Kataoka H
  • Organizer: 99th Annual Meeting of American Association of Cancer Research
  • Place of Presentation: SanDiego CA, USA.
  • Year and Date: 2008-04-14