2003 年度研究成果報告書概要

星細胞と線維化肝で発現する新遺伝子stapの分子機能と臨床病態的意義の解析

研究課題

研究課題/領域番号	14570497
研究種目	基盤研究(C)
配分区分	補助金
応募区分	一般
研究分野	消化器内科学
研究機関	大阪市立大学
研究代表者	河田則文大阪市立大学, 大学院・医学研究科, 講師 (30271191)
研究分担者	池田一雄大阪市立大学, 大学院・医学研究科, 講師 (80275247) 関守一大阪市立大学, 大学院・医学研究科, 助教授 (50145778)
研究期間 (年度)	2002 – 2003
キーワード	サイトグロビン / ヘモグロビン / ビタミンA貯蔵細胞 / 星細胞 / 臓器線維化
研究概要	1998年より星細胞に発現する蛋白質を網羅的に解析するためにプロテオームプロジェクトをおこない、ラット活性化星細胞に特異的に発現する分子群を同定した(Kristensen DB, Kawada N, et al. Hepatology 32:268, 2000)。この過程で今回の研究の主体となったstellate cell activation-associated protein (STAP)を発見した(Kawada N, Kristensen DB, et al. J Biol Chem, 276, 25318-25323, 2001)。さらに、ヒト星細胞株からヒトSTAPもクローニングした(Asahina K, Kawada N, et al. Biochim Biophys Acta 1577:471, 2002)。STAPは新しいグロビン蛋白でありcytoglobin (Cygb)と命名された。Cygb/STAPは酸素結合能をもつ。肝臓のみでなく、膵臓や腎臓の線維芽細胞にも発現することが判明した(Nakatani K, Okuyama H, et al. Lab Invest, 84, 91-101, 2004)。Cygb/STAPは星細胞の活性化とともに発現上昇し、内蔵臓器の線維化に重要な役割を果たす事が示唆されている。Cygb/STAPの結晶解析の結果、この蛋白はhexa-coordinate globinであり、ミオグロビンやヘモグロビンとは酸素との親和性が異なる可能性が示唆された。既に、種々の動物のCygb/STAP cDNAをクローニングしており、今後、蛋白独自の機能解析へと移行したい。

研究成果

(27件)

すべてその他

すべて文献書誌 (27件)

[文献書誌] Nakatani K, Okuyama H, et al.: "Cytoglobin/STAP, its unique localization in splanchnic fibroblast-like cells and function in organ fibrogenesis."Lab Invest.. 84. 91-101 (2004)
- 説明
  「研究成果報告書概要(和文)」より
[文献書誌] Uyama N, Shimahara Y, et al.: "Carbenoxolone inhibits DNA synthesis and collagen gene expression in rat hepatic stellate cells in culture."J Hepatol.. 39. 749-755 (2003)
- 説明
  「研究成果報告書概要(和文)」より
[文献書誌] Inagaki Y, Nemoto T, et al.: "Interferon alfa down-regulates collagen gene transcription and suppresses experimental hepatic fibrosis in mice."Hepatology. 38. 890-899 (2003)
- 説明
  「研究成果報告書概要(和文)」より
[文献書誌] Sawai H, Kawada N, et al.: "Characterization of the heme environmental structure of cytoglobin, a fourth globin in humans."Biochemistry. 42. 5133-5142 (2003)
- 説明
  「研究成果報告書概要(和文)」より
[文献書誌] Maeda N, Kawada N, et al.: "Stimulation of proliferation of rat hepatic stellate cells by galectin-1 and galectin-3 through different intracellular signaling pathways."J Biol Chem.. 278. 18938-18944 (2003)
- 説明
  「研究成果報告書概要(和文)」より
[文献書誌] Asahina K, Kawada N, et al.: "Characterization of human stellate cell activation-associated protein and its expression in human liver."Biochim Biophys Acta.. 1577. 471-475 (2002)
- 説明
  「研究成果報告書概要(和文)」より
[文献書誌] Asahina K, Kawada N, Kristensen DB, Nakatani K, Seki S, Shiokawa M, Tateno C, Obara M, Yoshizato K.: "Characterization of Human stellate cell activation-associated protein and its expression in human liver"Biochim Biophys Acta. 1577(3). 471-475 (2002)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Takashima T, Kawada N, Maeda N, Okuyama H, Uyama N, Seki S, Arakawa T.: "Pepstatin A attenuates the inhibitory effect of N-acetyl-L-cysteine on proliferation of hepatic myofibroblasts (stellate cells)"Eur J Pharmacol. 451(3). 265-270 (2002)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Akita K, Okuno M, Enya M, Imai S, Moriwaki H, Kawada N, Suzuki Y, Kojima S.: "Impaired liver regeneration in mice by lipopolysaccharide via TNF-alpha/kallikrein-mediated activation of latent TGF-beta"Gastroenterology. 1223(1). 352-364 (2002)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Seki S, Kitada T, Kawada N, Kadoya H, Sakaguchi H, Nakatani K, Satake K.: "Fatty change in human hepatocellular carcinoma cell lines derived from patients with antibodies to hepatitis C virus"Hepatogastroenterology. 49(44). 340-344 (2002)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Uyama N, Shimahara Y, Kawada N, Seki S, Okuyama H, Iimuro Y, Yamaoka Y.: "Regulation of cultured rat hepatocyte proliferation by stellate cells"J Hepatol. 36(5). 590-599 (2002)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Okuyama H, Shimahara Y, Kawada N.: "The hepatic stellate cell in the post-genomic era"Histol Histopathol. 17(2). 487-495 (2002)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Nakatani K, Seki S, Kawada N, Kitada T, Yamada T, Sakaguchi H, Kadoya H, Ikeda K, Kaneda K.: "Expression of SPARC by activated hepatic stellate cells and its correlation with the stages of fibrogenesis in human chronic hepatitis"Virchows Arch. 441(5). 466-474 (2002)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Seki S, Kitada T, sakaguchi H, Iwai S, Kawada N, Hayashi Y, Kim SR: "Expression of progenitor cell markers in livers with fulminant massive necrosis"Hepatol Res. 25(2). 149-157 (2003)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Sawai H, Kawada N, Yoshizato K, Nakajima H, Aono S, Shiro Y.: "Characterization of the heme environmental structure of cytoglobin, a fourth globin in humans"Biochemistry. 42(17). 5133-5142 (2003)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Okuyama H, Nakamura H, Shimahara Y, Araya S, Kawada N, Yamaoka Y, Yodoi J.: "Overexpression of thioredoxin prevents acute hepatitis caused by thioacetamide or lipopolysaccharide in mice"Hepatology. 37(5). 353-364 (2003)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Kobayashi S, Seki S, Kawada N, Morikawa H, Nakatani K, Uyama N, Ikeda K, Nakajima Y, Arakawa T, Kaneda K.: "Apoptosis of T cells in the hepatic fibrotic tissue of the rat: a possible inducing role of hepatic myofibroblast-like cells"Cell Tissue Res. 311(3). 353-364 (2003)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Maeda N, Kawada N, Seki S, Arakawa T, Ikeda K, Iwao H, Okuyama H, Hirabayashi J, Kasai K, Yoshizato K: "Stimulation of proliferation of rat hepatic stellate cells by galectin-1 and galectin-3 through different intracellular signaling pathways"J Biol Chem. 278(21). 18938-18944 (2003)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Seki s, Kitada T, Iwai S, Kadoya H, Yamada T, Kawada N, Sakaguchi H, Wakasa K: "Immunohistochemical detection of Fas and apoptosis in type-1 autoimmune hepatitis"Hepatogastroenterology. 50(53). 1274-1277 (2003)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Uyama N, shimahara Y, Okuyama H, kawada N, Kamo S, Ikeda K, Yamaoka Y.: "Carbenoxolone inhibits DNA synthesis and collagen gene expression in rat hepatic stellate cells in culture"J Hepatol. 39(5). 749-755 (2003)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Inagaki Y, Nemoto T, Kushida M, Sheng Y, Higashi K, Ikeda K, Kawada N, Shirasaki F, Takehara K, Sugiyama K, fujii M, Yamauchi H, Nakao A, de Crombrugghe B, Watanabe T, Okazaki I.: "Interferon alfa down-regulates collagen gene transcription and suppresses experimental hepatic fibrosis in mice"Hepatology. 38(4). 890-899 (2003)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Imanishi Y, Maeda N, Matsui H, Takashima T, Seki S, Arakawa T, Kawada N.: "Suppression of Rat Stellate Cell Activation and Liver Fibrosis by a Japanese Herbal Medicine, Inchinko-to (TJ135)"Comp Hepatol. 3 Suppl 1. S11 (2004)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Maeda N, Kawada N, Seki S, Ikeda K, Okuyama H, Hirabayashi J, Kasai KI, Yoshizato K.: "Involvement of Galectin-1 and Galectin-3 in Proliferation and Migration of Rat Hepatic Stellate Cells in Culture"Comp Hepatol. 3 Suppl 1. S10 (2004)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Matsui H, Takashima T, Maeda N, Imanishi Y, Uyama N, Okuyama H, Kawada N.: "Amino acids, L-Cysteine and L-Methionine, Attenuate Activation of Rat Stellate Cells in Primary Culture"Comp Hepatol. 3 Suppl 1. S9 (2004)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Okuyama H, shimahara Y, Nakamura H, Araya S, Kawada N, Yamaoka Y, Yodoi J.: "Thioredoxin prevents thioacetamide-induced acute hepatitis"Comp Hepatol. 3 Suppl 1. S6 (2004)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Kawada N.: "Molecular mechanism of stellate cell activation and therapeutic strategy for liver fibrosis"Comp Hepatol (No abstract available). 3 Suppl 1. S3 (2004)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Nakatani K, Okuyama H, Shimahara Y, Saeki S, Kim DH, Nakajima Y, Seki S, Kawada N, Yoshizato K.: "Cytoglobin/STAP, its unique localization in splanchnic fibroblast-like cells and function in organ fibrogenesis"Lab Invest. 84(1). 91-101 (2004)
- 説明
  「研究成果報告書概要(欧文)」より

2003 年度 研究成果報告書概要

星細胞と線維化肝で発現する新遺伝子stapの分子機能と臨床病態的意義の解析

研究代表者

河田 則文 大阪市立大学, 大学院・医学研究科, 講師 (30271191)

研究成果

[文献書誌] Nakatani K, Okuyama H, et al.: "Cytoglobin/STAP, its unique localization in splanchnic fibroblast-like cells and function in organ fibrogenesis."Lab Invest.. 84. 91-101 (2004)

説明

[文献書誌] Uyama N, Shimahara Y, et al.: "Carbenoxolone inhibits DNA synthesis and collagen gene expression in rat hepatic stellate cells in culture."J Hepatol.. 39. 749-755 (2003)

説明

[文献書誌] Inagaki Y, Nemoto T, et al.: "Interferon alfa down-regulates collagen gene transcription and suppresses experimental hepatic fibrosis in mice."Hepatology. 38. 890-899 (2003)

説明

[文献書誌] Sawai H, Kawada N, et al.: "Characterization of the heme environmental structure of cytoglobin, a fourth globin in humans."Biochemistry. 42. 5133-5142 (2003)

説明

[文献書誌] Maeda N, Kawada N, et al.: "Stimulation of proliferation of rat hepatic stellate cells by galectin-1 and galectin-3 through different intracellular signaling pathways."J Biol Chem.. 278. 18938-18944 (2003)

説明

[文献書誌] Asahina K, Kawada N, et al.: "Characterization of human stellate cell activation-associated protein and its expression in human liver."Biochim Biophys Acta.. 1577. 471-475 (2002)

説明

[文献書誌] Asahina K, Kawada N, Kristensen DB, Nakatani K, Seki S, Shiokawa M, Tateno C, Obara M, Yoshizato K.: "Characterization of Human stellate cell activation-associated protein and its expression in human liver"Biochim Biophys Acta. 1577(3). 471-475 (2002)

説明

[文献書誌] Takashima T, Kawada N, Maeda N, Okuyama H, Uyama N, Seki S, Arakawa T.: "Pepstatin A attenuates the inhibitory effect of N-acetyl-L-cysteine on proliferation of hepatic myofibroblasts (stellate cells)"Eur J Pharmacol. 451(3). 265-270 (2002)

説明

[文献書誌] Akita K, Okuno M, Enya M, Imai S, Moriwaki H, Kawada N, Suzuki Y, Kojima S.: "Impaired liver regeneration in mice by lipopolysaccharide via TNF-alpha/kallikrein-mediated activation of latent TGF-beta"Gastroenterology. 1223(1). 352-364 (2002)

説明

[文献書誌] Seki S, Kitada T, Kawada N, Kadoya H, Sakaguchi H, Nakatani K, Satake K.: "Fatty change in human hepatocellular carcinoma cell lines derived from patients with antibodies to hepatitis C virus"Hepatogastroenterology. 49(44). 340-344 (2002)

説明

[文献書誌] Uyama N, Shimahara Y, Kawada N, Seki S, Okuyama H, Iimuro Y, Yamaoka Y.: "Regulation of cultured rat hepatocyte proliferation by stellate cells"J Hepatol. 36(5). 590-599 (2002)

説明

[文献書誌] Okuyama H, Shimahara Y, Kawada N.: "The hepatic stellate cell in the post-genomic era"Histol Histopathol. 17(2). 487-495 (2002)

説明

[文献書誌] Nakatani K, Seki S, Kawada N, Kitada T, Yamada T, Sakaguchi H, Kadoya H, Ikeda K, Kaneda K.: "Expression of SPARC by activated hepatic stellate cells and its correlation with the stages of fibrogenesis in human chronic hepatitis"Virchows Arch. 441(5). 466-474 (2002)

説明

[文献書誌] Seki S, Kitada T, sakaguchi H, Iwai S, Kawada N, Hayashi Y, Kim SR: "Expression of progenitor cell markers in livers with fulminant massive necrosis"Hepatol Res. 25(2). 149-157 (2003)

説明

[文献書誌] Sawai H, Kawada N, Yoshizato K, Nakajima H, Aono S, Shiro Y.: "Characterization of the heme environmental structure of cytoglobin, a fourth globin in humans"Biochemistry. 42(17). 5133-5142 (2003)

説明

[文献書誌] Okuyama H, Nakamura H, Shimahara Y, Araya S, Kawada N, Yamaoka Y, Yodoi J.: "Overexpression of thioredoxin prevents acute hepatitis caused by thioacetamide or lipopolysaccharide in mice"Hepatology. 37(5). 353-364 (2003)

説明

[文献書誌] Kobayashi S, Seki S, Kawada N, Morikawa H, Nakatani K, Uyama N, Ikeda K, Nakajima Y, Arakawa T, Kaneda K.: "Apoptosis of T cells in the hepatic fibrotic tissue of the rat: a possible inducing role of hepatic myofibroblast-like cells"Cell Tissue Res. 311(3). 353-364 (2003)

説明

[文献書誌] Maeda N, Kawada N, Seki S, Arakawa T, Ikeda K, Iwao H, Okuyama H, Hirabayashi J, Kasai K, Yoshizato K: "Stimulation of proliferation of rat hepatic stellate cells by galectin-1 and galectin-3 through different intracellular signaling pathways"J Biol Chem. 278(21). 18938-18944 (2003)

説明

[文献書誌] Seki s, Kitada T, Iwai S, Kadoya H, Yamada T, Kawada N, Sakaguchi H, Wakasa K: "Immunohistochemical detection of Fas and apoptosis in type-1 autoimmune hepatitis"Hepatogastroenterology. 50(53). 1274-1277 (2003)

説明

[文献書誌] Uyama N, shimahara Y, Okuyama H, kawada N, Kamo S, Ikeda K, Yamaoka Y.: "Carbenoxolone inhibits DNA synthesis and collagen gene expression in rat hepatic stellate cells in culture"J Hepatol. 39(5). 749-755 (2003)

説明

説明

[文献書誌] Imanishi Y, Maeda N, Matsui H, Takashima T, Seki S, Arakawa T, Kawada N.: "Suppression of Rat Stellate Cell Activation and Liver Fibrosis by a Japanese Herbal Medicine, Inchinko-to (TJ135)"Comp Hepatol. 3 Suppl 1. S11 (2004)

説明

[文献書誌] Maeda N, Kawada N, Seki S, Ikeda K, Okuyama H, Hirabayashi J, Kasai KI, Yoshizato K.: "Involvement of Galectin-1 and Galectin-3 in Proliferation and Migration of Rat Hepatic Stellate Cells in Culture"Comp Hepatol. 3 Suppl 1. S10 (2004)

説明

[文献書誌] Matsui H, Takashima T, Maeda N, Imanishi Y, Uyama N, Okuyama H, Kawada N.: "Amino acids, L-Cysteine and L-Methionine, Attenuate Activation of Rat Stellate Cells in Primary Culture"Comp Hepatol. 3 Suppl 1. S9 (2004)

説明

[文献書誌] Okuyama H, shimahara Y, Nakamura H, Araya S, Kawada N, Yamaoka Y, Yodoi J.: "Thioredoxin prevents thioacetamide-induced acute hepatitis"Comp Hepatol. 3 Suppl 1. S6 (2004)

説明

[文献書誌] Kawada N.: "Molecular mechanism of stellate cell activation and therapeutic strategy for liver fibrosis"Comp Hepatol (No abstract available). 3 Suppl 1. S3 (2004)

説明

[文献書誌] Nakatani K, Okuyama H, Shimahara Y, Saeki S, Kim DH, Nakajima Y, Seki S, Kawada N, Yoshizato K.: "Cytoglobin/STAP, its unique localization in splanchnic fibroblast-like cells and function in organ fibrogenesis"Lab Invest. 84(1). 91-101 (2004)

説明

2003 年度研究成果報告書概要

河田則文大阪市立大学, 大学院・医学研究科, 講師 (30271191)