Role of membrane-bound serine protease inhibitor in maintaining integrity of intestinal epithelium

• Project/Area Number: 23790250
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General physiology
• Research Institution: University of Miyazaki
• Principal Investigator: KAWAGUCHI Makiko 宮崎大学, 医学部, 助教 (90405598)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 腸上皮 / セリンプロテアーゼ / 細胞膜結合型セリンプロテアーゼインヒビター / 上皮機能 / プロテアーゼ / 病理学

Research Abstract

To analyze the role of HAI-1 in intestine, we used intestinal tissue-specific HAI-1 conditional deficient mice. We found morphological abnormalities in the colonic epithelium with enhanced epithelial cell apoptosis and increased mucosal permeability. Moreover, mice lacking intestinal HAI-1 showed significantly enhanced susceptibility to colitis induced by dextran sodium sulfate (DSS) exposure. These results suggest that HAI-1/SPINT1 plays an important role in maintaining colonic epithelium integrity.

Research Products

• [Journal Article] Hepatocyte growth factor activator inhibitor type 1 is a suppressor of intestinal tumorigenesis (2013)
  • Author(s): Hoshiko S, Kawaguchi M, Fukushima T, Haruyama Y, Yorita Y, Tanaka H, Seiki M, Inatsu H, Kitamura K, Kataoka H
  • Journal Title: Cancer Res Volume: 73 Pages: 2659-2670
  • Peer Reviewed
• [Journal Article] Regulation of pericellular proteolysis by hepatocyte growth factor activator inhibitor type 1 (HAI-1) in trophoblast cells (2013)
  • Author(s): Kohama K, Kawaguchi M, Fukushima T, Lin C-Y, Kataoka H
  • Journal Title: Hum. Cell Volume: 25 Pages: 100-110
  • Peer Reviewed
• [Journal Article] Regulation of pericellular proteolysis by hepatocyte growth factor activator inhibitor type 1 (HAI-1) in trophoblast cells. (2013)
  • Author(s): Kohama K, Kawaguchi M, Fukushima T, Lin C-Y, Kataoka H.
  • Journal Title: Human Cell Volume: 25 Issue: 4 Pages: 100-110
  • DOI: 10.1007/s13577-012-0055-2
  • Peer Reviewed
• [Journal Article] Loss of membrane-bound serine protease inhibitor HAI-1 induces oral squamous cell carcinoma cells invasiveness (2012)
  • Author(s): Baba T, Kawaguchi M, Fukushima T, Sato Y, Orikawa H,Yorita K,Tanaka H,Lin C-Y, Sakoda S, Kataoka H
  • Journal Title: J. Pathol Volume: 228 Pages: 181-192
  • Peer Reviewed
• [Journal Article] Activation of macrophage-stimulating protein by human airway trypsin-like protease (2012)
  • Author(s): Orikawa H, Kawaguchi M, Baba T, Yorita K, Sakoda S, Kataoka H
  • Journal Title: FEBS Lett Volume: 586 Pages: 217-221
  • Peer Reviewed
• [Journal Article] Antitumor effect of dehydroxymethylepoxyquinomicin (DHMEQ),a small molecule inhibitor of nuclear factor-kB, on glioblastoma. (2012)
  • Author(s): Fukushima T, Kawaguchi M, Yorita K, Tanaka H, Umezawa K, Takeshima H, Kataoka H
  • Journal Title: Neuro. Oncol Volume: 14 Pages: 19-28
  • Peer Reviewed
• [Journal Article] Loss of membrane-bound serine protease inhibitor HAI-1 inducesoral squamous cell carcinoma cells' invasiveness (2012)
  • Author(s): Baba T, Kawaguchi M, Fukushima T, Sato Y, Orikawa H, Yorita K, Tanaka H, Lin CY, Sakoda S, Kataoka H
  • Journal Title: J Pathol Volume: (Epub ahead of print) Issue: 2 Pages: 181-192
  • DOI: 10.1002/path.3993
  • Peer Reviewed
• [Journal Article] Activation of macrophage-stimulating protein by human airway trypsin-like protease (2012)
  • Author(s): Orikawa H, Kawaguchi M, Baba T, Yorita K, Sakoda S, Kataoka H
  • Journal Title: FEBS Letters Volume: 586 Issue: 3 Pages: 217-221
  • DOI: 10.1016/j.febslet.2012.01.009
  • Peer Reviewed
• [Journal Article] Membrane-bound serine protease inhibitor HAI-1 is required for maintenance of intestinal epithelial integrity (2011)
  • Author(s): Kawaguchi M, Takeda N, Hoshiko S, Yorita K, Baba T, Sawaguchi A, Nezu Y, Yoshikawa T, Fukushima T, Kataoka H
  • Journal Title: Am. J. Pathol Volume: 179 Pages: 1815-1826
  • Peer Reviewed
• [Journal Article] Membrane-bound serine protease inhibitor HAI-1 is required for maintenance of intestinal epithelial integrity (2011)
  • Author(s): Kawaguchi M, Takeda N, Hoshiko S, Yorita K, Baba T, Sawaguchi A, Nezu Y, Yoshikawa T, Fukushima T, Kataoka H
  • Journal Title: American Journal of Pathology Volume: 179 Issue: 4 Pages: 1815-1826
  • DOI: 10.1016/j.ajpath.2011.06.038
  • Peer Reviewed
• [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 Volume: 102 Issue: 2 Pages: 407-413
  • DOI: 10.1111/j.1349-7006.2010.01808.x
  • NAID: 10029290246
  • Peer Reviewed
• [Presentation] Ye JJ, Kawaguchi M, Haruyama Y, Kanemaru A, Fukushima T, Kataoka H (2013)
  • Author(s): Ye JJ, Kawaguchi M, Haruyama Y, Kanemaru A, Fukushima T, Kataoka H
  • Organizer: An AACR Special Conference on Tumor Invasion and Metastasis.
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2013-01-21
• [Presentation] Hepatocyte growth factor activator inhibitor type 1 (HAI-1) suppresses tumor growth and metastasis of pancreatic adenocarcinoma cells. (2013)
  • Author(s): Jing-Jia Ye, Makiko Kawaguchi, Yukihiro Haruyama, Ai Kanemaru,Tsuyoshi Fukushima, Hiroaki Kataoka
  • Organizer: An AACR Special Conference on Tumor Invasion and Metastasis
  • Place of Presentation: San Diego, USA
• [Presentation] HGF activator inhibitor type 1 (HAI-1) suppresses tumor growth and metastasis of pancreatic adenocarcinoma cells (2012)
  • Author(s): Kawaguchi M, Haruyama Y, Kataoka H
  • Organizer: 第71回日本癌学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 2012-09-21
• [Presentation] 細胞膜結合型プロテアーゼインヒビターHAI-1 は 表皮角化細胞の形態形成に必須である (2012)
  • Author(s): 川口 真紀子、竹田直樹、星子新理、福島剛、片岡寛章
  • Organizer: 第17回 日本病態プロテアーゼ学会学術集会
  • Place of Presentation: 浜松
  • Year and Date: 2012-08-17
• [Presentation] 膜型プロテアーゼインヒビターHAI-1 による口腔扁平上皮癌の浸潤制御 (2012)
  • Author(s): 片岡寛章、馬場貴、福島剛、川口真紀子、迫田隅男
  • Organizer: 第21回日本がん転移学会学術集会
  • Place of Presentation: 広島
  • Year and Date: 2012-07-21
• [Presentation] 細胞膜結合型プロテアーゼインヒビター HAI-1 は 表皮角化細胞の形態形成に必須である (2012)
  • Author(s): 川口 真紀子、竹田直樹、星子新理、福島剛、片岡寛章
  • Organizer: 第17回 日本病態プロテアーゼ学会学術集会
  • Place of Presentation: 浜松市
• [Presentation] HGF activator inhibitor type 1 (HAI-1) suppresses tumor growth and metastasis of pancreatic adenocarcinoma cells. (2012)
  • Author(s): Makiko Kawaguchi, Yukihiro Haruyama, Hiroaki Kataoka
  • Organizer: 第71回日本癌学会学術集会
  • Place of Presentation: 札幌市
• [Presentation] Hepatpcyte growth factoractivator inhibitor type 1 (HAI-1) regulates cell morphology through control of the actin cytoskeleton in epidermal keratinocyte (2011)
  • Author(s): Kawaguchi M, Takeda N, Sawaguchi A, Sato Y, Hoshiko S, Fukushima T, Kataoka H
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-15
• [Presentation] Type II membrane-type serine protease, matriptase, is expressed in perivascular tumor cells HLC-1 xenograft (2011)
  • Author(s): Kawaguchi M, Baba T, Fukushi ma T, Kataoka H
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-03
• [Presentation] 細胞 膜結合型セリンプロテアーゼインヒビターHepatocyte growth factor activator inhibitor type 1 (HAI-1) は腸上皮完全性維持に必須である (2011)
  • Author(s): 川口真紀子、竹田直樹、星子新理、頼田顕辞、馬場貴、澤口朗、福島剛、片岡寛章
  • Organizer: 第16回日本病態プロテアーゼ学会学術総会
  • Place of Presentation: 豊中
  • Year and Date: 2011-08-26
• [Presentation] Hepatocyte growth factor activator inhibitor type 1 (HAI-1) plays an important role in maintaining integrity of intestinal epithelium (2011)
  • Author(s): Kawaguchi M, Hoshiko S, Yorita K, Baba T, Fukushima T, Kataoka H
  • Organizer: XlIIth International Workshop on Molecular & Cellular Biology of Plasminogen Activation
  • Place of Presentation: Cambridge, UK
  • Year and Date: 2011-07-10
• [Presentation] Defect of hepatocyte growth factor activator inhibitor type1, a cell surface serine protease inhibitor (2011)
  • Author(s): Hoshiko S, Kawaguchi M, Yorita K, Fukushima T, Kataoka H
  • Organizer: enhances intestinal tumorigenesis in ApcMin/+ mice
  • Place of Presentation: Chicago, USA
  • Year and Date: 2011-05-10
• [Presentation] Hepatocyte growth factor activator inhibitor type 1 (HAI-1) は 表皮角化細胞の形態形成を制御している (2011)
  • Author(s): 川口真紀子、星子新理、福島 剛、田中弘之、頼田 顕辞、梅北 佳子、片岡 寛章
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2011-04-29
• [Presentation] Hepatocyte growth factor activator inhibitor type 1 (HAI-1) plays an important role in maintaining integrity of intestinal epithelium. (2011)
  • Author(s): Kawaguchi M, Hoshiko S, Yorita K, Baba T, Fukushima T, Kataoka H
  • Organizer: XlIIth International Workshop on Molecular & Cellular Biology of Plasminogen Activation
  • Place of Presentation: Clare College, Cambridge, UK
• [Presentation] 細胞膜結合型セリンプロテアーゼインヒビター、Hepatocyte growth factor activator inhibitor type 1 (HAI-1) は腸上皮完全性維持に必須である (2011)
  • Author(s): 川口真紀子、竹田直樹、星子新理、頼田顕辞、馬場貴、澤口朗、福島剛、片岡寛章
  • Organizer: 第16回日本病態プロテアーゼ学会学術集会
  • Place of Presentation: 千里ライフサイエンスセンター（大阪府）