1996 年度研究成果報告書概要

レチノイド拮抗剤による肝線維化抑制効果に関する研究

研究課題

研究課題/領域番号	06670534
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	岐阜大学
研究代表者	奥野正隆岐阜大学, 医学部・附属病院, 助手 (10204140)
研究分担者	森脇久隆岐阜大学, 医学部, 助教授 (50174470)
研究期間 (年度)	1994 – 1996
キーワード	肝線維化 / レチノイド / transforming growth factor-β / 伊東細胞 / コラーゲン
研究概要	肝線維化に関与する伊東細胞は、障害肝においてレチノイドを失いコラーゲンを大量に産生する細胞へと形質転換する事が知られている。我々は、この形質転換の過程で新規レチノイン酸である9, 13-di-cis-レチノイン酸(dcRA)が増加する事を発見した。dcRAは転写活性を有し、伊東細胞において、プラスミノゲンアクティベータ(PA)を誘導し、プラスミンを活性化させて、transforming growth factor (TGF) -βを活性化させることを明らかにした。TGF-βは、伊東細胞自身を刺激し、コラーゲン合成を亢進させる。この際、dcRAはレチノイド核レセプターの一つであるretinoic acid receptor (RAR) αを介して、この一連の誘導を行う事も明らかにした。従ってRAR αとdcRAの結合を阻害しするレチノイドアンタゴニストは、TGF-βの活性化を抑制し、肝線維化の治療薬となり得る可能性を秘めている。我々は、RAR α選択的なアンタゴニストや、RAR αβγ全てを阻害するpanアンタゴニストを用いた研究を行いない有望な化合物を得ることが出来た。

研究成果
(24件)

すべてその他

すべて文献書誌 (24件)

[文献書誌] Numaguchi S, Okuno M et al.: "Modulation of collagen synthesis and degradation by retinoids and cytokines in 3T3L1 preadiptcytes" Int Med. 33. 309-316 (1994)
- 説明
  「研究成果報告書概要(和文)」より
[文献書誌] Okuno M, Moriwaki H, et al.: "Changes in the ratio of branched-chain to aromatic amino acids affect the secretion of albumin in cultured rat hepatocytes" Biochem Biophys Res Commun. 214. 1045-1050 (1995)
- 説明
  「研究成果報告書概要(和文)」より
[文献書誌] Okuno M, Caraueo VE, et al.: "Regulation of gene expression by retinoic acid and hormones : effects on the gene encoding cellular retinol-binding protein" J Lipid Res. 36. 137-147 (1995)
- 説明
  「研究成果報告書概要(和文)」より
[文献書誌] Miwa Y, Okuno M, et al.: "Effects of branched-chain amino acid infusion on protein metabolism in rats with acute hepatic failure" Hepatology. 22. 291-296 (1995)
- 説明
  「研究成果報告書概要(和文)」より
[文献書誌] Iwamine T, Okuno M, et al.: "Impaired synthesis of retinol-binding protein and trans thyretin in rat liver with obstractive jaundice" Dig Dis Sci. 41. 1038-1042 (1996)
- 説明
  「研究成果報告書概要(和文)」より
[文献書誌] Usui T, Okuno M, et al.: "Oral supplementation with branched-chain amino acids improves trans thyretin turnover in rats with CCl_4-induced liver cirrhosis" J Nutr. 126. 1412-1420 (1996)
- 説明
  「研究成果報告書概要(和文)」より
[文献書誌] Muto Y, Okuno M, et al.: "Prevention of second primary tumor by a retinoid, polyprenoic acid, in patients with hepato cellular carcinoma" N Engl J Med. 334. 1561-1567 (1996)
- 説明
  「研究成果報告書概要(和文)」より
[文献書誌] Katsumura N, Okuno M, et al.: "Suppression of mouse skin papilloma by canthaxanthin and β-carotene in vivo" Nutr Cancer. 26. 203-206 (1996)
- 説明
  「研究成果報告書概要(和文)」より
[文献書誌] Onogi N, Okuno M, et al.: "Suppressing effect of perilla oil on azoxymethane-induced foci of colonic aberrant crypts in rats." Carcinogenesis. 17. 1291-1296 (1996)
- 説明
  「研究成果報告書概要(和文)」より
[文献書誌] Koda H, Okuno M, et al.: "Retinoic acid-stimulated liver stellate cells suppress the production of albumin from parenchymal cells via TGF-β." Biochem Biophys Res Commun. 221. 565-569 (1996)
- 説明
  「研究成果報告書概要(和文)」より
[文献書誌] Komaki C, Okuno M, et al.: "Synergistic suppression of azoxymethane-induced foci of aberrant crypts by the combmation of β-carotene and perilla oil in rats" Carcinogenesis. 17. 1897-1901 (1996)
- 説明
  「研究成果報告書概要(和文)」より
[文献書誌] Moriwaki H, Okuno M, et al.: "Deletion of serum lectin-reactive α-fetoprotein by acyctic retinoid : a potent biomarker in the chemoprevention of second hepatoma" Clin Cancer Res. (in press).
- 説明
  「研究成果報告書概要(和文)」より
[文献書誌] Numaguchi S,Okuno M,Moriwaki H,Muto Y.: "Modulation of collagen synthesis and degradation by retinoids and cytokines in 3T3L1 preadipocytes." Int Med. 33. 309-316 (1994)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Okuno M,Moriwaki H,Kato M,Muto Y,Kojima S.: "Changes in the ratio of branched-chain to aromatic amino acids affect the secretion of albumin in cultured rat hepatocytes." Biochem Biophys Res Commun. 214. 1045-1050 (1995)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Okuno M,Caraveo VE,Goodman DS,Blaner WS.: "Regulation of adipocyte gene expression by retinoic acid and hormones : effects on the gene encoding cellular retinol-binding protein." J Lipid Res. 36. 137-147 (1995)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Miwa Y,Kato M,Moriwaki H,Okuno, M,Sugihara J,Ohnishi H,Yoshida T,Muto Y,Nakayama M,Morioka Y,Asagi K.: "Effects of branched-chain amino acid infusion on protein metabolism in rats with acute hepatic failure." Hepatology. 22. 291-296 (1995)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Imamine T,Okuno M,Moriwaki H,Shidoji Y,Muto Y,Seishima M,Noma A,Kojima S.: "Impaired synthesis of retinol-binding protein and transthyretin in rat liver with obstructive jaundice." Dig Dis Sci. 41. 1038-1042 (1996)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Usui T,Moriwaki H,Hatakeyama H,Kanai T,Kato M,Okuno M,Ohnishi H,Yoshida T, Muto Y.: "Oral supplementation with branched-chain amino acids improves transthyretin turnover in rats with carbon tetrachloride-induced liver cirrhosis." J Nutr. 126. 1412-1420 (1996)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Muto Y,Moriwaki H,Ninomiya M,Adachi S,Saito A,Takasaki KT,Tanaka T,Tsurumi K,Okuno M,Uematsu T,Tomita E,Nakamura T,Kojima T.: "Prevention of secondary primary tumors by a retinoid, polyprenoic acid, in patients with hepatocellular carcnoma." N Eng J Med. 334. 1561-1567 (1996)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Katsumura N,Okuno M,Onogi N,Moriwaki H,Muto Y,Kojima S.: "Suppresion of mouse skin papilloma by canthaxanthin and beta-carotene in vivo : possibility of the regulation of tumorigenesis by carotenoids without being converted to retinoic acid." Nutr Cancer. 26. 203-206 (1996)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Onogi N,Okuno M,Komaki C,Moriwaki H,Kawamori T,Tanaka T,Mori H,Muto Y.: "Suppressing effect of perilla oil on azoxymethane-induced foci of colonic aberrant crypts in rats." Carcinogenesis. 17. 1291-1296 (1996)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Koda H,Okuno M,Imai S,Moriwaki H,Muto Y,Kawada N,Kojima S.: "Retinoic acid-stimulated liver stellate cells suppress the production of albumin from parenchymal cells via TGF-beta." Biochem Biophys Res Commun. 221. 565-569 (1996)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Komaki C,Okuno M,Onogi N,Moriwaki H,Kawamori T,Tanaka T,Mori H,Muto Y.: "Synergistic suppression of azoxymethane-induced foci of abberant crypts by the combination ofbeta-carotene and perilla oil in rats." Carcinigenesis. 17. 1897-1901 (1996)
- 説明
  「研究成果報告書概要(欧文)」より
[文献書誌] Moriwaki H,Yasuda I,Shiratori Y,Uematsu T,Okuno M,Muto Y.: "Deletion of serum lectin-reactive alpha-fetoprotein by acyclic retinoid : a potent biomarker in the chemoprevention of second primary hepatoma." Clin Cancer Res. (in press).
- 説明
  「研究成果報告書概要(欧文)」より

1996 年度 研究成果報告書概要

レチノイド拮抗剤による肝線維化抑制効果に関する研究

研究代表者

奥野 正隆 岐阜大学, 医学部・附属病院, 助手 (10204140)

研究成果

[文献書誌] Numaguchi S, Okuno M et al.: "Modulation of collagen synthesis and degradation by retinoids and cytokines in 3T3L1 preadiptcytes" Int Med. 33. 309-316 (1994)

説明

[文献書誌] Okuno M, Moriwaki H, et al.: "Changes in the ratio of branched-chain to aromatic amino acids affect the secretion of albumin in cultured rat hepatocytes" Biochem Biophys Res Commun. 214. 1045-1050 (1995)

説明

[文献書誌] Okuno M, Caraueo VE, et al.: "Regulation of gene expression by retinoic acid and hormones : effects on the gene encoding cellular retinol-binding protein" J Lipid Res. 36. 137-147 (1995)

説明

[文献書誌] Miwa Y, Okuno M, et al.: "Effects of branched-chain amino acid infusion on protein metabolism in rats with acute hepatic failure" Hepatology. 22. 291-296 (1995)

説明

[文献書誌] Iwamine T, Okuno M, et al.: "Impaired synthesis of retinol-binding protein and trans thyretin in rat liver with obstractive jaundice" Dig Dis Sci. 41. 1038-1042 (1996)

説明

[文献書誌] Usui T, Okuno M, et al.: "Oral supplementation with branched-chain amino acids improves trans thyretin turnover in rats with CCl_4-induced liver cirrhosis" J Nutr. 126. 1412-1420 (1996)

説明

[文献書誌] Muto Y, Okuno M, et al.: "Prevention of second primary tumor by a retinoid, polyprenoic acid, in patients with hepato cellular carcinoma" N Engl J Med. 334. 1561-1567 (1996)

説明

[文献書誌] Katsumura N, Okuno M, et al.: "Suppression of mouse skin papilloma by canthaxanthin and β-carotene in vivo" Nutr Cancer. 26. 203-206 (1996)

説明

[文献書誌] Onogi N, Okuno M, et al.: "Suppressing effect of perilla oil on azoxymethane-induced foci of colonic aberrant crypts in rats." Carcinogenesis. 17. 1291-1296 (1996)

説明

[文献書誌] Koda H, Okuno M, et al.: "Retinoic acid-stimulated liver stellate cells suppress the production of albumin from parenchymal cells via TGF-β." Biochem Biophys Res Commun. 221. 565-569 (1996)

説明

[文献書誌] Komaki C, Okuno M, et al.: "Synergistic suppression of azoxymethane-induced foci of aberrant crypts by the combmation of β-carotene and perilla oil in rats" Carcinogenesis. 17. 1897-1901 (1996)

説明

[文献書誌] Moriwaki H, Okuno M, et al.: "Deletion of serum lectin-reactive α-fetoprotein by acyctic retinoid : a potent biomarker in the chemoprevention of second hepatoma" Clin Cancer Res. (in press).

説明

[文献書誌] Numaguchi S,Okuno M,Moriwaki H,Muto Y.: "Modulation of collagen synthesis and degradation by retinoids and cytokines in 3T3L1 preadipocytes." Int Med. 33. 309-316 (1994)

説明

[文献書誌] Okuno M,Moriwaki H,Kato M,Muto Y,Kojima S.: "Changes in the ratio of branched-chain to aromatic amino acids affect the secretion of albumin in cultured rat hepatocytes." Biochem Biophys Res Commun. 214. 1045-1050 (1995)

説明

[文献書誌] Okuno M,Caraveo VE,Goodman DS,Blaner WS.: "Regulation of adipocyte gene expression by retinoic acid and hormones : effects on the gene encoding cellular retinol-binding protein." J Lipid Res. 36. 137-147 (1995)

説明

[文献書誌] Miwa Y,Kato M,Moriwaki H,Okuno, M,Sugihara J,Ohnishi H,Yoshida T,Muto Y,Nakayama M,Morioka Y,Asagi K.: "Effects of branched-chain amino acid infusion on protein metabolism in rats with acute hepatic failure." Hepatology. 22. 291-296 (1995)

説明

[文献書誌] Imamine T,Okuno M,Moriwaki H,Shidoji Y,Muto Y,Seishima M,Noma A,Kojima S.: "Impaired synthesis of retinol-binding protein and transthyretin in rat liver with obstructive jaundice." Dig Dis Sci. 41. 1038-1042 (1996)

説明

[文献書誌] Usui T,Moriwaki H,Hatakeyama H,Kanai T,Kato M,Okuno M,Ohnishi H,Yoshida T, Muto Y.: "Oral supplementation with branched-chain amino acids improves transthyretin turnover in rats with carbon tetrachloride-induced liver cirrhosis." J Nutr. 126. 1412-1420 (1996)

説明

[文献書誌] Muto Y,Moriwaki H,Ninomiya M,Adachi S,Saito A,Takasaki KT,Tanaka T,Tsurumi K,Okuno M,Uematsu T,Tomita E,Nakamura T,Kojima T.: "Prevention of secondary primary tumors by a retinoid, polyprenoic acid, in patients with hepatocellular carcnoma." N Eng J Med. 334. 1561-1567 (1996)

説明

[文献書誌] Katsumura N,Okuno M,Onogi N,Moriwaki H,Muto Y,Kojima S.: "Suppresion of mouse skin papilloma by canthaxanthin and beta-carotene in vivo : possibility of the regulation of tumorigenesis by carotenoids without being converted to retinoic acid." Nutr Cancer. 26. 203-206 (1996)

説明

[文献書誌] Onogi N,Okuno M,Komaki C,Moriwaki H,Kawamori T,Tanaka T,Mori H,Muto Y.: "Suppressing effect of perilla oil on azoxymethane-induced foci of colonic aberrant crypts in rats." Carcinogenesis. 17. 1291-1296 (1996)

説明

[文献書誌] Koda H,Okuno M,Imai S,Moriwaki H,Muto Y,Kawada N,Kojima S.: "Retinoic acid-stimulated liver stellate cells suppress the production of albumin from parenchymal cells via TGF-beta." Biochem Biophys Res Commun. 221. 565-569 (1996)

説明

[文献書誌] Komaki C,Okuno M,Onogi N,Moriwaki H,Kawamori T,Tanaka T,Mori H,Muto Y.: "Synergistic suppression of azoxymethane-induced foci of abberant crypts by the combination ofbeta-carotene and perilla oil in rats." Carcinigenesis. 17. 1897-1901 (1996)

説明

[文献書誌] Moriwaki H,Yasuda I,Shiratori Y,Uematsu T,Okuno M,Muto Y.: "Deletion of serum lectin-reactive alpha-fetoprotein by acyclic retinoid : a potent biomarker in the chemoprevention of second primary hepatoma." Clin Cancer Res. (in press).

説明

1996 年度研究成果報告書概要

奥野正隆岐阜大学, 医学部・附属病院, 助手 (10204140)