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Analysis of liver regeneration : A study using c-kit mutants

Research Project

Project/Area Number13670232
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Experimental pathology
Research InstitutionHyogo College of Medicine

Principal Investigator

TSUJIMURA Tohru  Hyogo College of Medicine Department of Pathology Associate Professor, 医学部, 助教授 (20227408)

Co-Investigator(Kenkyū-buntansha) HISHIDA Shigeru  Hyogo College of Medicine Department of Legal Medicine Professor, 医学部, 教授 (10068463)
TERADA Nobuyuki  Hyogo College of Medicine Department of Pathology Professor, 医学部, 教授 (50150339)
Project Period (FY) 2001 – 2002
Project Status Completed(Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost : ¥3,600,000)
Fiscal Year 2002 : ¥1,400,000 (Direct Cost : ¥1,400,000)
Fiscal Year 2001 : ¥2,200,000 (Direct Cost : ¥2,200,000)
Keywordsc-kit receptor tyrosine kinase / transplantation / W / W^v mice / sinusoid endothelial cells / liver regeneration / Ws / Ws rats / liver development / bile epithelial cells
Research Abstract

We examined whether bone marrow (BM) cells can commit to liver-consisting cells during liver regeneration. BM cells of green fluorescent protein (GFP) transgenic mice were transplanted into W/W^v c-kit mutant mice after whole-body irradiation. In the resulting W/W^v (BMT-W/W^v) mice, GFP positive cells were observed at the periportal region. When CCl_4 or anti-Fas antibody was administered to BMT-W/W^v mice, GFP positive cells developed along liver sinusoid. These results suggest that BM cells differentiate to sinusoid endothelial cells during liver regeneration.
Recently, it has been shown that the expression of c-kit receptor tyrosine kinase (KIT) is seen in the liver of young rats, and its expression is up-regulated in bile epithelial cells (BEC) after ligation of the common bile duct (BDL). To clarify a role of KIT in BEC, we examined whether BEC of Ws/Ws c-kit mutant rats could proliferate in response to bile stasis after BDL. When 2-week-old normal (+/+) and Ws/Ws rats underwent BDL, only a few BEC were found in the portal field of livers of Ws/Ws rats, whereas many BBC were found in that of +/+ rats. Furthermore, Ki-67 immunostaining showed that the proliferative activity of BEC in 2-week-old Ws/Ws rats was much lower than that of +/+ rats of the same age. In contrast, when 6-week-old +/+ and Ws/Ws rats underwent BDL, BEC similarly proliferated in the livers of +/+ and Ws/Ws rats, and the proliferative activity of BEC was comparable. It is likely that the mechanism whereby BEC proliferate in response to bile stasis after BDL is different between 2-week-old and 6-week-old rats, and KIT mediated-signal transduction plays a crucial role in the proliferation of immature BEC in young rats.

Report

(3results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report

Research Products

(53results)

All Other

All Publications

  • [Publications] Iwasaki T et al.: "Involvement of phosphorylation of Tyr-31 and Tyr-118 of paxillin in MM1 cancer cell migration"Int J Cancer. 97. 330-335 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takagi-Morishita Y et al.: "Castration induces apoptosis in the mouse epididymis during postnatal development"Endocr J. 49. 75-84 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ueda S et al.: "Critical roles of c-Kit tyrosine residues 567 and 719 in stem cell factor-induced chemotaxis : contribution of src family kinase and PI3-kinase on calcium mobilization and cell migration"Blood. 99. 3342-3349 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kitanaka J et al.: "Expression of diamine oxidase (histaminase) in guinea-pig tissues"Eur J Pharmacol. 437. 179-185 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwasaki T et al.: "Interleukin-18 inhibits osteolytic bone metastasis by human lung cancer cells possibly through suppression of osteoclastic bone-resorption in nude mice"J Immunother. 25 Suppl 1. S52-S60 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamada N et al.: "Interleukin-18 and Interleukin-12 synergistically inhibit osteoclastic bone-resorbing activity"Bone. 30. 901-908 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwasaki T et al.: "Ipriflavone inhibits osteolytic bone metastasis of human breast cancer cells in a nude-mice model"Int J Cancer. 100. 381-387 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sarlomo-Rikala M et al.: "Patterns of nestin and other intermediate filament expression distinguish between gastrointestinal stromal tumors, leiomyomas and schwannomas"APMIS. 110. 499-507 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamashita K et al.: "Interleukin-18 inhibits lodging and subsequent growth of human multiple myeloma cells in the bone marrow"Oncol Rep. 9. 1237-1244 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hashimoto K et al.: "Necessity of tyrosine 719 and phosphatidylinositol 3'-kinase-mediated signal pathway in constitutive activation and oncogenic potential of c-kit receptor tyrosine kinase with the D814V mutation"Blood. 101. 1094-1102 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sanjo H et al.: "TAB2 is essential for prevention of apoptosis in fetal liver but not for IL-1 signaling"Mol Cell Biol. 23. 1231-1238 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takagi-Morishita Y et al.: "Mouse uterine epithelial apoptosis is associated with expression of mitochondrial voltage-dependent anion channels, release of cytochrome C from mitochondria, and the ratio of bax to bcl-2 or bcl-x"Biol Reprod. 68. 1178-1184 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tanimizu N et al.: "Ipriflavone inhibits osteolytic bone metastasis of human breast cancer cells in a nude-mice model"J Cell Sci. 116. 1775-1786 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Satake M et al.: "Role of c-kit receptor tyrosine kinase-mediated signal transduction in proliferation of bile epithelial cells in young rats after ligation of bile duct : A study using Ws/Ws c-kit mutant rats"J Hepatol. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Simano K et al.: "Hepatic oval cells have the side population phenotype defined by expression of ATP-binding cassette transporter ABCG2/BCRP1"Am J Pathol. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwasaki T, Nakata A, Mukai M, Shinkai K, Yano H, Sabe H, Schaefer E, Tatsuta M, Tsujimura T, Terada N, Kakishita E, Akedo H: "Involvement of phosphorylation of Tyr-31 and Tyr-118 of paxillin in MM1 cancer cell migration"Int J Cancer. 97. 330-335 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ueda S, Mizuki M, Ikeda H, Tsujimura T, Matsumura I, Nakano K, Daino H, Honda Z-I, Sonoyama J, Shibayama H, Sugahara H, Machii T, Kanakura Y: "Critical roles of c-Kit tyrosine residues 567 and 719 in stem cell factor-induced chemotaxis : contribution of src family kinase and PI3-kinase on calcium mobilization and cell migration"Blood. 99. 3342-3349 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takagi-Morishita Y, Kuhara A, Sugihara A, Yamada N, Yamamoto R, Iwasaki T, Tsujimura T, Tanji N, Terada N: "Castration induces apoptosis in the mouse epididymis during postnatal development"Endocr J. 49. 75-84 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kitanaka J, Kitanaka N, Tsujimura T, Terada N, Takemura M: "Expression of diamine oxidase (histaminase) in guinea-pig tissues"Eur J Pharmacol. 437. 179-185 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamashita K, Iwasaki T, Tsujimura T, Sugihara A, Yamada N, Ueda H, Okamura H, Futani H, Maruo S, Terada N: "Interleukin-18 inhibits lodging and subsequent growth of human multiple myeloma cells in the bone marrow"Oncol Rep. 9. 1237-1244 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwasaki T, Yamashita K, Tsujimura T, Kashiwamura S-I, Tsutsui H, Kaisho T, Sugihara A, Yamada N, Mukai M, Yoneda T, Okamura H, Akedo H, Terada N: "Interleukin-18 inhibits osteolytic bone metastasis by human lung cancer cells possibly through suppression of osteoclastic bone-resorption in nude mice"J Immunother. 25 Suppl 1. S52-S60 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamada N, Niwa S, Tsujimura T, Iwasaki T, Sugihara A, Futani H, Hayashi S, Okamura H, Akedo H, Terada N: "Interleukin-18 and Interleukin-12 synergistically inhibit osteoclastic bone-resorbing activity"Bone. 30. 901-908 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwasaki T, Mukai M, Tsujimura T, Tatsuta M, Nakamura H, Terada N, Akedo H: "Ipriflavone inhibits osteolytic bone metastasis of human breast cancer cells in a nude-mice model"Int J Cancer. 100. 381-387 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sarlomo-Rikala M, Tsujimura T, Lendahl U, Miettinen M: "Patterns of nestin and other intermediate filament expression distinguish between gastrointestinal stromal tumors, leiomyomas and schwannomas"APMIS. 110. 499-507 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hashimoto K, Matsumura I, Tsujimura T, Kim D-K, Ogihara H, Ikeda H, Ueda S, Mizuki M, Sugawara H, Shibayama H, Kitamura Y, Kanakura Y: "Necessity of tyrosine 719 and phosphatidylinositol 3'-kinase-mediated signal pathway in constitutive activation and oncogenic potential of c-kit receptor tyrosine kinase with the D814V mutation"Blood. 101. 1094-1102 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sanjo H, Takeda K, Tsujimura T, Ninomiya-Tsuji J, Matsumoto K, Akira S: "TAB2 is essential for prevention of apoptosis in fetal liver but not for IL-1 signaling"Mol Cell Biol. 23. 1231-1238 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takagi-Morishita Y, Yamada N, Sugihara A, Iwasaki T, Tsujimura T, Terada N: "Mouse uterine epithelial apoptosis is associated with expression of mitochondrial voltage-dependent anion channels, release of cytochrome C from mitochondria, and the ratio of bax to bcl-2 or bcl-x"Biol Reprod. 68. 1178-1184 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tanimizu N, Nishikawa M, Saito H, Tsujimura T, Miyajima A: "Isolation of hepatoblasts based on the expression of Dlk/Pref-1"J Cell Sci. 116. 1775-1786 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Satake M, Shimano K, Yamamoto T, Okaya A, Iwasaki T, Kakihana M, Fujimoto J, Terada N, Tsujimura T: "Role of c-kit receptor tyrosine kinase-mediated signal transduction in proliferation of bile epithelial cells in young rats after ligation of bile duct : A study using Ws/Ws c-kit mutant rats"J Hepatol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Shimano K, Satake M, Okaya A, Kitanaka J, Kitanaka N, Takemura M, Sakagami M, Terada N, Tsujimura T: "Hepatic oval cells have the side population phenotype defined by expression of ATP-binding cassette transporter ABCG2/BCRP1"Am J Pathol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Iwasaki T et al.: "Involvement of phosphorylation of Tyr-31 and Tyr-118 of paxillin in MM1 cancer cell migration"Int J Cancer. 97. 330-335 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takagi-Morishita Y et al.: "Castration induces apoptosis in the mouse epididymis during postnatal development"Endocr J. 49. 75-84 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ueda S et al.: "Critical roles of c-Kit tyrosine residues 567 and 719 in stem cell factor-induced chemotaxis : contribution of src family kinase and PI3-kinase on calcium mobilization and cell migration"Blood. 99. 3342-3349 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kitanaka J et al.: "Expression of diamine oxidase (histaminase) in guinea-pig tissues"Eur J Pharmacol. 437. 178-185 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iwasaki T et al.: "Interleukin-18 inhibits osteolytic bone metastasis by human lung cancer cells possibly through suppression of osteoclastic bone-resorption in nude mice"J Immunother. 25 Suppl 1. S52-S60 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamada N et al.: "Interleukin-18 and Interleukin-12 synergistically inhibit osteoclastic bone-resorbing activity"Bone. 30. 901-908 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Iwasaki T et al.: "Ipriflavone inhibits osteolytic bone metastasis of human breast cancer cells in a nude-mice model"Int J Cancer. 100. 381-387 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sarlomo-Rikala M et al.: "Patterns of nestin and other intermediate filament expression distinguish between gastrointestinal stromal tumors, leiomyomas and schwannomas"APMIS. 110. 499-507 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamashita K et al.: "Interleukin-18 inhibits lodging and subsequent growth of human multiple myeloma cells in the bone marrow"Oncol Rep. 9. 1237-1244 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hashimoto K et al.: "Necessity of tyrosine 719 and phosphatidylinositol 3'-kinase-mediated signal pathway in constitutive activation and oncogenic potential of c-kit receptor tyrosine kinase with the D814V mutation"Blood. 101. 1094-1102 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sanjo H et al.: "TAB2 is essential for prevention of apoptosis in fetal liver but not for IL-1 signaling"Mol Cell Biol. 23. 1231-1238 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kaisho T et al.: "IκB kinase α is essential for mature B cell development and function"J Exp Med. 193・4. 417-426 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tsujimura T et al.: "Expression of the intermediate filament nestin in gastrointestinal stromal tumors and interstitial cells of cajal"Am J Pathol. 158・3. 817-823 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Makiishi-Shimobayashi C et al.: "Interleukin-18 up-regulates osteoprotegerin expression in stromal/osteoblastic cells"Biochem Biophys Res Commun. 281・2. 361-366 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Makiishi-Shimobayashi C et al.: "Expression of osteopontin by exudate macrophages in inflammatory tissues of the middle ear : a possible association with development of tympanosclerosis"Hear Res. 153・1-2. 100-107 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kitanaka J et al.: "Guinea pig histamine N-methyltransferase : cDNA cloning and mRNA distribution"Jpn J Pharmacol. 85・1. 105-108 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kitanaka J et al.: "Histamine N-methyltransferase regulates histamine-induced phosphoinositide hydrolysis in guinea pig cerebellum"Neurosci Lett. 308・1. 5-8 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sugihara A et al.: "Castration induces apoptosis in the male accessory sex organs of Fas-deficient lpr and Fas ligand-deficient gld mutant mice"In Vivo. 15・5. 385-390 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Iwasaki T et al.: "Involvement of phosphorylation of Tyr-31 and Tyr-118 of paxillin in MM1 cancer cell migration"Int J Cancer. 97・3. 330-335 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sugihara A et al.: "Primary carcinoid tumor of the urinary bladder"Int Urol Nephrol. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Ueda S et al.: "Critical roles of c-kit tyrosine residues 567 and 719 in stem cell factor-induced chemotaxis : contribution of src family kinase and P13-kinase on calcium mobilization and cell migration"Blood. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Takagi Y et al.: "Castration induces apoptosis in the mouse epididymis during postnatal development"Endocrine J. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamada N et al.: "Interleukin-18 and interleukin-12 synergistically inhibit osteoclastic bone-resorbing activity"Bone. (in press).

    • Related Report
      2001 Annual Research Report

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Published : 2001-04-01   Modified : 2016-04-21  

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