2000 Fiscal Year Annual Research Report

血管内皮増殖因子(VEGF)は重症肝炎、劇症肝炎の治療薬となり得るか

Research Project

Project/Area Number	09670588
Research Institution	Fukuoka University
Principal Investigator	向坂彰太郎福岡大学, 医学部, 教授 (90158923)
Keywords	VEGF / 肝再生 / 類洞内皮細胞 / 肝細胞
Research Abstract	近年、癌細胞の増殖や組織の創傷治癒にangiogenesisが重要な働きをしていることが明らかにされ、VEGFはその中心的役割を果たしていると考えられている。我々は再生肝において、主に門脈域周囲の肝細胞がVEGFを産生し、血管系の再構築に関与している可能性を示してきた。本年、我々はVEGFが肝再生においてどのような役割を担っているかを検討するため、ラットの70%肝切除による肝再生モデルに、抗VEGF中和抗体およびVEGFタンパクを投与し、類洞内皮細胞および肝細胞の増殖を検討した。類洞内皮細胞の増殖は抗VEGF中和抗体投与群では有意にその増殖が抑制され、またVEGFタンパク投与群では有意にその増殖が増進された。さらに肝細胞の増殖においても抗VEGF中和抗体群では有意にその増殖が抑制され、VEGFタンパク投与群では有意にその増殖が増進された。また肝切除後のラット肝におけるVEGFのm-RNAの発現をin situ hybridizationにより検討したところ、門脈域周囲の肝細胞に強い発現がみられた。これらの結果から、再生肝においては肝細胞から産生されたVEGFが類洞内皮細胞の増殖を促し、類洞の再構築を行うことで肝細胞への血流増加が起こり、肝細胞の増殖が増進されることが示唆された。

Research Products
(9 results)

All Other

All Publications (9 results)

[Publications] Shotaro Sakisaka: "Ursodeoxycholic acid reduces expression of heat shock proteins in primary biliary cirrhosis"Liver. 20・1. 78-87 (2000)
[Publications] Masaru Harada: "Role of ATP7B in biliary copper-excretion in a human hepatoma cell line and normal rat hepatocytes"Gastroenterology. 118・5. 921-928 (2000)
[Publications] Masaru Harada: "High prevalence of anticardiolipin antibodies in hepatitis C virus infection : lack of effects on thrombocytopenia and thrombotic complications"J Gastroenterol. 35・4. 272-277 (2000)
[Publications] Takumi Kawaguchi: "Cholestasis with altered structure and function of hepatocyte tight junction and decreased expression of canalicular multispecific organic anion transporter in a rat model of colitis"Hepatology. 31・6. 1285-1295 (2000)
[Publications] Masaru Harada: "Copper does not alter the intracellular distribution of ATP7B, a copper-transporting ATPase"Biochem Biophys Res Commun. 275・3. 871-876 (2000)
[Publications] Eitaro Taniguchi: "Expression and Role of Vascular Endothelial Growth Factor in Liver Regeneration After Partial Hepatectomy in Rats"J Histochem Cytochem. 49・1. 121-130 (2001)
[Publications] Masaru Harada: "A Mutation of Wilson's disease protein, ATP7B, Is Degraded in the Proteasomes and Forms Protein Aggregates"Gastroenterology. (in press). (2001)
[Publications] Takumi Kawaguchi: "Endotoxin Increases Paracellular Permeability of Isolated Rat Hepatocyte Couplets"Hepatology Research. (in press). (2001)
[Publications] Shotaro Sakisaka: "Alterations in Tight Junction Differ between Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis"Hepatology. (in press). (2001)

2000 Fiscal Year Annual Research Report

血管内皮増殖因子(VEGF)は重症肝炎、劇症肝炎の治療薬となり得るか

Principal Investigator

向坂 彰太郎 福岡大学, 医学部, 教授 (90158923)

Research Products

[Publications] Shotaro Sakisaka: "Ursodeoxycholic acid reduces expression of heat shock proteins in primary biliary cirrhosis"Liver. 20・1. 78-87 (2000)

[Publications] Masaru Harada: "Role of ATP7B in biliary copper-excretion in a human hepatoma cell line and normal rat hepatocytes"Gastroenterology. 118・5. 921-928 (2000)

[Publications] Masaru Harada: "High prevalence of anticardiolipin antibodies in hepatitis C virus infection : lack of effects on thrombocytopenia and thrombotic complications"J Gastroenterol. 35・4. 272-277 (2000)

[Publications] Takumi Kawaguchi: "Cholestasis with altered structure and function of hepatocyte tight junction and decreased expression of canalicular multispecific organic anion transporter in a rat model of colitis"Hepatology. 31・6. 1285-1295 (2000)

[Publications] Masaru Harada: "Copper does not alter the intracellular distribution of ATP7B, a copper-transporting ATPase"Biochem Biophys Res Commun. 275・3. 871-876 (2000)

[Publications] Eitaro Taniguchi: "Expression and Role of Vascular Endothelial Growth Factor in Liver Regeneration After Partial Hepatectomy in Rats"J Histochem Cytochem. 49・1. 121-130 (2001)

[Publications] Masaru Harada: "A Mutation of Wilson's disease protein, ATP7B, Is Degraded in the Proteasomes and Forms Protein Aggregates"Gastroenterology. (in press). (2001)

[Publications] Takumi Kawaguchi: "Endotoxin Increases Paracellular Permeability of Isolated Rat Hepatocyte Couplets"Hepatology Research. (in press). (2001)

[Publications] Shotaro Sakisaka: "Alterations in Tight Junction Differ between Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis"Hepatology. (in press). (2001)

向坂彰太郎福岡大学, 医学部, 教授 (90158923)