1991 年度実績報告書

肝傷害に伴うHGF(肝細胞増殖因子)の発現誘導と発現誘導因子の実体解明

研究課題

研究課題/領域番号	03680173
研究機関	九州大学
研究代表者	松本邦夫九州大学, 理学部, 助手 (90201780)
研究分担者	中村敏一九州大学, 理学部, 教授 (00049397)
キーワード	肝細胞増殖因子 / HGF / 肝再生 / 腎再生 / 増殖因子
研究概要	1.肝傷害、腎傷害に伴う遠隔無傷臓器におけるHGFの発現誘導:ラットにCCl_4肝炎を誘発すると肝非実質細胞においてHGF mRNAの著しい発現誘導がみられ、HGFはパラクリン機構で肝再生を促すことを、既に報告した。一方、本年度において、肝傷害に伴い、傷害を受けた肝臓とは離れた肺、腎臓、脾臓、においても、速やかなHGF mRNAの発現誘導がみられること、さらに、肝傷害(部分肝切除)後血中HGF活性が速やかに増加することを見い出した。これらの結果は、肺、腎臓、脾臓など無傷の臓器で産生されたHGFがエンドクリン機構で肝臓の再生に関与すること、さらに肝傷害に伴い、他の無傷臓器におけるHGF mRNAの発現を誘導する何らかのメディエ-タ-が存在することを示唆している。 2.HGF発現誘導因子の精製:肝傷害を引き起こしたラットの血清を、別の正常ラットに投与し、肺におけるHGF mRNAを解析したところ、正常血清を投与した場合に比べ、HGF mRNAの発現が増加した。このことは、肝傷害ラット血中に肺におけるHGFの発現を誘導する因子が存在することを示している。私達は本因子を、傷害″injury″をメディエ-トすることからインジュリンと名付けた。一方、ヒト胎児肺由来線維芽細胞MRCー5に肝傷害ラット血清を添加すると、MRCー5によるHGF産生量が増加することを見出し、MRCー5を用いるin vitroのアッセイ系がインジュリンの精製のための有効なアッセイ系となることを確認した。このアッセイ系を用いて、肝傷害ラット血清中から2段階のクロマトグラフィ-を行い、インジュリンを約200倍に部分精製した。インジュリンは分子量10〜30kDの蛋白質性の因子であると考えられた。

研究成果
(34件)

すべてその他

すべて文献書誌 (34件)

[文献書誌] K.Matsumoto and T.Nakamura: "Hepatocyte growth factor:molecular structure and implications for a central role in liver regeneration." J.Gastroenterol.Hepatol.6. 509-519 (1991)
[文献書誌] M.Hashiro,K.Matsumoto,H.Okumura,K.Hashimoto,and K.Yoshikawa: "Growth inhibition of human keratinocyte by antisence cーmycoligomer is not coupled to induction of differentiation" Biochem.Biophys.Res.Commun.174. 287-292 (1991)
[文献書誌] K.Matsumoto,H.Tajima,and T.Nakamura: "Hepatocyte growth factor is a potent stimulator of human melanocyte DNA synthesis and growth." Biochem.Biophys.Res.Commun.176. 45-51 (1991)
[文献書誌] K.Matsumoto,Y.Azuma,M.Kiyoki,H.Okumura,K.Hashimoto,and K.Yoshikawa: "Involvement of endogenously produced 1,25ーdihydroxyvitamin D_3 in the growth and differentiation of human keratinocytes." Biochim.Biophys.Acta.1092. 311-318 (1991)
[文献書誌] M.Higashiyama,K.Matsumoto,K.Hashimoto,and K.Yoshikawa: "Increased production of transforming growth factorーalpha in psoriatic epidermis." J.Dermatol.117-119 (1991)
[文献書誌] T.Kinoshita,S.Hirao,K.Matsumoto,and T.Nakamura: "Possible endocrine control by hepatocyte growth factor of liver regeneration after partial hepatectomy." Biochem.Biophys.Res.Commun.177. 330-335 (1991)
[文献書誌] M.Nagaike,S.Hirao,H.Tajima,S.Noji,S.Taniguchi,K.Matsumoto,and T.Nakamura: "Renotropic function of hepatocyte growth factor in renal regeneration after unilateral unilateral nephrectomy." J.Biol.Chem.22781-22784 (1991)
[文献書誌] K.Matsumoto and T.Nakamura: "Hepatocyte growth factor:molecular structure,roles in liver regeneration,and other biological functions." Critical Rev.Oncogenesis. 3. 27-54 (1992)
[文献書誌] K.Matsumoto and T.Nakamura: "Role of hepatocyte growth factor in liver regeneration." In Cellular and Molecular Basis of Liver Cirrhosis(Inserm/Eurotext). 255-264 (1992)
[文献書誌] K.Matsumoto,K.Hashimoto,K.Yoshikawa,and T.Nakamura: "Marked stimulation of growth and motility of human keratinocytes by hepatocyte growth factor." Exp.Cell Res.196. 114-120 (1991)
[文献書誌] H.Tajima,K.Matsumto,and T.Nakamuara: "Hepatocyte growth factor has a potent antiーproliferative activity for various tumor cell lines." FEBS Lett.291. 229-232 (1991)
[文献書誌] "Identification of a fibroblastーderived epithelial morphogen as hepatocyte growth factor." Cell. 67. 901-908 (1991)
[文献書誌] M.Hashiro,K.Matsumoto,K.Hashimoto,and K.Yoshikawa: "Stimulation of fibronectin secretion in cultured human keratinocytes by transforming growth factorーbeta not by other growth inhibitory substances." J.Dermatol.18. 252-257 (1991)
[文献書誌] T.Konishi,T.Takehara,T.Tsuji,K.Ohsato,K.Matsumoto,and T.Nakamura: "Scatter factor from human embryonic lung fibroblasts is probably identical to hepatocyte growth factor." Biochem.Biophys.Res.Commun.180. 765-773 (1991)
[文献書誌] K.Matsumoto,T.Takehara,H.Inoue,M.Hagiya,S.Shimizu and T.Nakamura: "Deletion of kringle domains or the Nーterminal hairpin structure in hepatocyte growth factor results in marked decrease in related biological activities." Biochem.Biophys.Res.Commun.181. 691-699 (1991)
[文献書誌] K.Yanagita,M.Nagaike,H.Ishibashi,Y.Niho,K.Matsumoto and T.Nakamura: "Lung may have an endocrine function producing hepatocyte growth factor in response to injury of distal organs." Biochem.Biophys.Res.Commun.802-809 (1992)
[文献書誌] M.Sugai,K.Hashimoto,A.Kikuchi,S.Inoue,H.Okumura,K.Matsumoto,Y.Goto,H.Ohgai,K.Moriishi,B.Shuto,K.Yoshikawa,H.Suginaka and Y.Takai: "Epidermal differentiation inhibitor(EDIN)ADPーribosylates small GTPーbinding protein and induces hyperplasia of epidermis." J.Biol.Chem.(1992)
[文献書誌] K.Matsumoto,H.Tajima,M.Hamanoue,S.Kono,T.Kinoshita and T.Nakamura: "Identification and characterization of ″injurin″,an inducer of the gene expression of hepatocyte growth factor." Proc.Natl.Acad.Sci.USA,89. (1992)
[文献書誌] H.Tajima,K.Matsumoto and T.Nakamura: "Regulation of cell growth and cell motility by hepatocyte growth factor and its receptor expression in various typespof cells." Exp.Cell Res.,submitted to publication.(1992)
[文献書誌] M.Hamanoue,K.Kawaida,S.Takao,H.Shimazu,S.Noji,K.Matsumoto and T.Nakamura: "Rapid and marked induction of HGF mRNA in liver and HGF activity in serum of rats after ischemic or crush liver injury." Hepatology. (1992)
[文献書誌] T.Takehara,K.Matsumoto and T.Nakamura: "Cell densityーdependent regulation of albumin synthesis and DNA synthesis in rat hepatocytes by hepatocyte growth factor." J.Biochem.(1992)
[文献書誌] Y.Ishiki,H.Ohnishi,Y.Muto,K.Matsumoto and T.Nakamura: "Direct evidence that hepatocyte growth factor is ahepatotrophic factor for liver regeneration and for potent antiーhepatitis action in vivo." Hepatology. (1992)
[文献書誌] M.Johnson,T.Nakamura,K.Matsumoto,K.Kochhar and A.Iyer: "HGFーinduced scattering and mitogenesis of normal mouse liver cells are independent events." FEBS Lett.(1992)
[文献書誌] M.S.Pepper,K.Matsumoto,T.Nakamura,L.Orci and R.Montesano: "Hepatocyte growth factor induces urokinaseーtype plasminogen activator and plasminogen activator inhibitorー1 in MDCK epithelial cells." J.Biol.Chem.(1992)
[文献書誌] T Igawa,S Kanda,H Kanetake,Y Saitoh,K Matsumoto,and T Nakamura: "Hepatocyte growth factor may function as a renotropic factor for regeneration in rats with acutely induced renal injury." Kidney International,submitted to publication.(1992)
[文献書誌] 松本邦夫,中村敏一: ""肝細胞増殖因子(HGF)の構造と機能"" 代謝. 28. 3-12 (1991)
[文献書誌] 木下大成,松本邦夫,中村敏一: ""HGFの多様な生理作用と組織再生"" 「サイトカインと情報伝達」実験医学. 144-153 (1992)
[文献書誌] K.Matsumoto and T.Nakamura: "Protocols In Cell & Tissue Culture,(Collagenase and Hyaluronidase)" John & Wiley, (1992)
[文献書誌] 堀田安男,大熊勝治編,松本邦夫,中村敏一: "肝細胞の培養法「細胞生物学実験法1」" 広川書店, (1992)
[文献書誌] 松本邦夫,中村敏一: ""肝細胞の培養法"細胞生物学実験法" 広川書店, (1992)
[文献書誌] 松本邦夫,中村敏一: "肝細胞「生物薬科学実験法」" 広川書店, (1992)
[文献書誌] 木下大成,松本邦夫,中村敏一: "肝細胞増殖因子(HGF)〜精製、アッセイ、応用〜「生物薬科学実験法」" 広川書店, (1992)
[文献書誌] 松本邦夫,中村敏一: "肝臓毒性「動物代替試験法」" 広川書店, (1992)
[文献書誌] 松本邦夫,中村敏一: "″HGI″細胞成長因子(日本組織培養学会編)" 朝倉書店, (1992)

1991 年度 実績報告書

肝傷害に伴うHGF(肝細胞増殖因子)の発現誘導と発現誘導因子の実体解明

研究代表者

松本 邦夫 九州大学, 理学部, 助手 (90201780)

研究成果

[文献書誌] K.Matsumoto and T.Nakamura: "Hepatocyte growth factor:molecular structure and implications for a central role in liver regeneration." J.Gastroenterol.Hepatol.6. 509-519 (1991)

[文献書誌] M.Hashiro,K.Matsumoto,H.Okumura,K.Hashimoto,and K.Yoshikawa: "Growth inhibition of human keratinocyte by antisence cーmycoligomer is not coupled to induction of differentiation" Biochem.Biophys.Res.Commun.174. 287-292 (1991)

[文献書誌] K.Matsumoto,H.Tajima,and T.Nakamura: "Hepatocyte growth factor is a potent stimulator of human melanocyte DNA synthesis and growth." Biochem.Biophys.Res.Commun.176. 45-51 (1991)

[文献書誌] K.Matsumoto,Y.Azuma,M.Kiyoki,H.Okumura,K.Hashimoto,and K.Yoshikawa: "Involvement of endogenously produced 1,25ーdihydroxyvitamin D_3 in the growth and differentiation of human keratinocytes." Biochim.Biophys.Acta.1092. 311-318 (1991)

[文献書誌] M.Higashiyama,K.Matsumoto,K.Hashimoto,and K.Yoshikawa: "Increased production of transforming growth factorーalpha in psoriatic epidermis." J.Dermatol.117-119 (1991)

[文献書誌] T.Kinoshita,S.Hirao,K.Matsumoto,and T.Nakamura: "Possible endocrine control by hepatocyte growth factor of liver regeneration after partial hepatectomy." Biochem.Biophys.Res.Commun.177. 330-335 (1991)

[文献書誌] M.Nagaike,S.Hirao,H.Tajima,S.Noji,S.Taniguchi,K.Matsumoto,and T.Nakamura: "Renotropic function of hepatocyte growth factor in renal regeneration after unilateral unilateral nephrectomy." J.Biol.Chem.22781-22784 (1991)

[文献書誌] K.Matsumoto and T.Nakamura: "Hepatocyte growth factor:molecular structure,roles in liver regeneration,and other biological functions." Critical Rev.Oncogenesis. 3. 27-54 (1992)

[文献書誌] K.Matsumoto and T.Nakamura: "Role of hepatocyte growth factor in liver regeneration." In Cellular and Molecular Basis of Liver Cirrhosis(Inserm/Eurotext). 255-264 (1992)

[文献書誌] K.Matsumoto,K.Hashimoto,K.Yoshikawa,and T.Nakamura: "Marked stimulation of growth and motility of human keratinocytes by hepatocyte growth factor." Exp.Cell Res.196. 114-120 (1991)

[文献書誌] H.Tajima,K.Matsumto,and T.Nakamuara: "Hepatocyte growth factor has a potent antiーproliferative activity for various tumor cell lines." FEBS Lett.291. 229-232 (1991)

[文献書誌] "Identification of a fibroblastーderived epithelial morphogen as hepatocyte growth factor." Cell. 67. 901-908 (1991)

[文献書誌] M.Hashiro,K.Matsumoto,K.Hashimoto,and K.Yoshikawa: "Stimulation of fibronectin secretion in cultured human keratinocytes by transforming growth factorーbeta not by other growth inhibitory substances." J.Dermatol.18. 252-257 (1991)

[文献書誌] T.Konishi,T.Takehara,T.Tsuji,K.Ohsato,K.Matsumoto,and T.Nakamura: "Scatter factor from human embryonic lung fibroblasts is probably identical to hepatocyte growth factor." Biochem.Biophys.Res.Commun.180. 765-773 (1991)

[文献書誌] K.Matsumoto,T.Takehara,H.Inoue,M.Hagiya,S.Shimizu and T.Nakamura: "Deletion of kringle domains or the Nーterminal hairpin structure in hepatocyte growth factor results in marked decrease in related biological activities." Biochem.Biophys.Res.Commun.181. 691-699 (1991)

[文献書誌] K.Yanagita,M.Nagaike,H.Ishibashi,Y.Niho,K.Matsumoto and T.Nakamura: "Lung may have an endocrine function producing hepatocyte growth factor in response to injury of distal organs." Biochem.Biophys.Res.Commun.802-809 (1992)

[文献書誌] M.Sugai,K.Hashimoto,A.Kikuchi,S.Inoue,H.Okumura,K.Matsumoto,Y.Goto,H.Ohgai,K.Moriishi,B.Shuto,K.Yoshikawa,H.Suginaka and Y.Takai: "Epidermal differentiation inhibitor(EDIN)ADPーribosylates small GTPーbinding protein and induces hyperplasia of epidermis." J.Biol.Chem.(1992)

[文献書誌] K.Matsumoto,H.Tajima,M.Hamanoue,S.Kono,T.Kinoshita and T.Nakamura: "Identification and characterization of ″injurin″,an inducer of the gene expression of hepatocyte growth factor." Proc.Natl.Acad.Sci.USA,89. (1992)

[文献書誌] H.Tajima,K.Matsumoto and T.Nakamura: "Regulation of cell growth and cell motility by hepatocyte growth factor and its receptor expression in various typespof cells." Exp.Cell Res.,submitted to publication.(1992)

[文献書誌] M.Hamanoue,K.Kawaida,S.Takao,H.Shimazu,S.Noji,K.Matsumoto and T.Nakamura: "Rapid and marked induction of HGF mRNA in liver and HGF activity in serum of rats after ischemic or crush liver injury." Hepatology. (1992)

[文献書誌] T.Takehara,K.Matsumoto and T.Nakamura: "Cell densityーdependent regulation of albumin synthesis and DNA synthesis in rat hepatocytes by hepatocyte growth factor." J.Biochem.(1992)

[文献書誌] Y.Ishiki,H.Ohnishi,Y.Muto,K.Matsumoto and T.Nakamura: "Direct evidence that hepatocyte growth factor is ahepatotrophic factor for liver regeneration and for potent antiーhepatitis action in vivo." Hepatology. (1992)

[文献書誌] M.Johnson,T.Nakamura,K.Matsumoto,K.Kochhar and A.Iyer: "HGFーinduced scattering and mitogenesis of normal mouse liver cells are independent events." FEBS Lett.(1992)

[文献書誌] M.S.Pepper,K.Matsumoto,T.Nakamura,L.Orci and R.Montesano: "Hepatocyte growth factor induces urokinaseーtype plasminogen activator and plasminogen activator inhibitorー1 in MDCK epithelial cells." J.Biol.Chem.(1992)

[文献書誌] T Igawa,S Kanda,H Kanetake,Y Saitoh,K Matsumoto,and T Nakamura: "Hepatocyte growth factor may function as a renotropic factor for regeneration in rats with acutely induced renal injury." Kidney International,submitted to publication.(1992)

[文献書誌] 松本 邦夫,中村 敏一: ""肝細胞増殖因子(HGF)の構造と機能"" 代謝. 28. 3-12 (1991)

[文献書誌] 木下 大成,松本 邦夫,中村 敏一: ""HGFの多様な生理作用と組織再生"" 「サイトカインと情報伝達」実験医学. 144-153 (1992)

[文献書誌] K.Matsumoto and T.Nakamura: "Protocols In Cell & Tissue Culture,(Collagenase and Hyaluronidase)" John & Wiley, (1992)

[文献書誌] 堀田 安男,大熊 勝治 編,松本 邦夫,中村 敏一: "肝細胞の培養法「細胞生物学実験法1」" 広川書店, (1992)

[文献書誌] 松本 邦夫,中村 敏一: ""肝細胞の培養法"細胞生物学実験法" 広川書店, (1992)

[文献書誌] 松本 邦夫,中村 敏一: "肝細胞「生物薬科学実験法」" 広川書店, (1992)

[文献書誌] 木下 大成,松本 邦夫,中村 敏一: "肝細胞増殖因子(HGF)〜精製、アッセイ、応用〜「生物薬科学実験法」" 広川書店, (1992)

[文献書誌] 松本 邦夫,中村 敏一: "肝臓毒性「動物代替試験法」" 広川書店, (1992)

[文献書誌] 松本 邦夫,中村 敏一: "″HGI″細胞成長因子(日本組織培養学会編)" 朝倉書店, (1992)

1991 年度実績報告書

松本邦夫九州大学, 理学部, 助手 (90201780)

[文献書誌] 松本邦夫,中村敏一: ""肝細胞増殖因子(HGF)の構造と機能"" 代謝. 28. 3-12 (1991)

[文献書誌] 木下大成,松本邦夫,中村敏一: ""HGFの多様な生理作用と組織再生"" 「サイトカインと情報伝達」実験医学. 144-153 (1992)

[文献書誌] 堀田安男,大熊勝治編,松本邦夫,中村敏一: "肝細胞の培養法「細胞生物学実験法1」" 広川書店, (1992)

[文献書誌] 松本邦夫,中村敏一: ""肝細胞の培養法"細胞生物学実験法" 広川書店, (1992)

[文献書誌] 松本邦夫,中村敏一: "肝細胞「生物薬科学実験法」" 広川書店, (1992)

[文献書誌] 木下大成,松本邦夫,中村敏一: "肝細胞増殖因子(HGF)〜精製、アッセイ、応用〜「生物薬科学実験法」" 広川書店, (1992)

[文献書誌] 松本邦夫,中村敏一: "肝臓毒性「動物代替試験法」" 広川書店, (1992)

[文献書誌] 松本邦夫,中村敏一: "″HGI″細胞成長因子(日本組織培養学会編)" 朝倉書店, (1992)