2000 Fiscal Year Annual Research Report

心停止者肝を肝移植ドナー・ソースとする方法の開発

Research Project

Project/Area Number	11470137
Research Institution	Saitama Medical University
Principal Investigator	藤原研司埼玉医科大学, 医学部, 教授 (80101088)
Co-Investigator(Kenkyū-buntansha)	松井淳埼玉医科大学, 医学部, 助手 (40260484) 名越澄子埼玉医科大学, 医学部, 講師 (50306271) 持田智埼玉医科大学, 医学部, 助教授 (20219968)
Keywords	VEGF / 肝類洞内皮細胞 / 肝星細胞 / 肝再生 / Angiopoietin / TIE受容体 / 肝移植後肝不全 / pericyte
Research Abstract	心停止者の肝を肝移植に用いる際には,脳死者の場合より重篤である類洞内皮細胞の障害を予防する必要がある。そこで,類洞内皮細胞の維持に必須であるVEGFの肝類洞に対する作用点を検討し,平成11年度は本因子が類洞内皮細胞の増殖を促進するのみならずporosityを増大させること,また,星細胞に対しては収縮を抑制するなど,血流調節にも寄与すること明かにした。この検討の過程で,類洞構造の維持には内皮細胞の維持,増殖のみでは不十分であり,pericyteである星細胞との相互作用により類洞を構築することが重要であることを見出した。平成12年度はこの点に関する検討を加えた。星細胞と類洞内皮細胞の相互作用に関わる因子としては,Angiopoietin(Ang)-1及び-2に注目した。Ang-1はpericyteの増殖と内皮細胞への裏打ち促進に,Ang-2はpericyteが血管からのdrop-outする過程に関与するとされる。70%部分切除ラット肝において,Ang-1,-2とその受容体であるTIE-1,-2の発現を定量的なcompetitive RT-PCRにより評価した。肝における両Angと受容体のmRNA発現は,VEGFの発現とほぼ一致して,類洞内皮細胞が増殖する時期の増強することを見出した。従って,類洞内皮細胞と星細胞が類洞を構築する過程でも,Ang・TIE受容体系が重要な役割を果たしている可能性がある。現在,免疫組織染色や単離肝構成細胞を用いたRT-PCRにより,Ang及びTIEの発現細胞を同定するとともに,その作用をin vitroで検討している。また,冷保存肝における検討も行い,類洞内皮細胞の保護に繋がるVEGFとAng系を介した治療法に関しても探索を行っている。

Research Products
(11 results)

All Other

All Publications (11 results)

[Publications] Osada N,Mochida S,Inao M,Mashimo Y,Fujiwara K.: "Apoptisis in dissociation between DNA synthesis and cellular functions of activated hepatic stellate cells : A study with carbon tetrachloride-induced rat liver injury."Biochemical Biophysical Research Communication. (In press). (2001)
[Publications] YouSuFu Y,Mochida S,Matsui A,Okamoto H,Fujiwara K.: "TT virus infection in cases of fulminant hepatic failure : Evaluation by clonality based on amino acid sequence of hypervariable regions."Hepatology Research. (In press). (2001)
[Publications] Niimi Y,Mochida S,Matsui A,Inao M,Fujiwara K.: "PKC- and MAPK-independent upregulation of VEGF receptor expressions in human umbilical venous endothelial cells following VEGF stimulation."Hepatology Research. (In press). (2001)
[Publications] Fujiwara K,Mochida S,Matsui A,Nagoshi S.: "Indication and criteria for liver transplantation for fulminant hepatic failure."J Gastroenterology and Hepatology. (In press). (2001)
[Publications] Funyu J,Mochida S,Inao M,Matsui A,Fujiwara K.: "VEGF can act as vascular permeability factor in the hepatic sinusoids through upregulation of porosity of endothelial cells."Biochemical Biophysical Research Communication. 280. 481-485 (2001)
[Publications] Mochida S,Fujiwara K.: "Recent advances in acute and fulminant hepatitis in Japan."Internal Medicine. 40. 175-177 (2001)
[Publications] Mochida S,Fujiwara K.: "Angiogenesis in the liver : A communication system among liver cells through VEGF."Connective Tissue. 32. 389-393 (2000)
[Publications] Ikeda H,Yatomi Y,Yanase M,Satoh H,Maekawa H,Ogata I,Ozaki Y,Takawa Y,Mochida S,Fujiwara K.: "Biological activities of novel lipid mediator sphingosine 1-phosphate in rat hepatic stellate cells."American Journal of Physiology. 279. G304-G310 (2000)
[Publications] Wang YH,Mochida S,Kawashima R,Inao M,Matsui A,YouLuTuz Y,Nagoshi S,Uede T,Fujiwara K.: "Increased expression of osteopontin in activated Kupffer cells and hepatic macrophages during macrophage migration in Propionibacterium acnes-treated rat liver."Journal of Gastroenterology. 35. 691-701 (2000)
[Publications] Mochida S,Fujiwara.: "Hepatic microcirculation in massive liver necrosis and liver regeneration. In : Gastroenterology and Hepatology : Millennium 2000"Asakura H (eds), Elsevier Science, Amsterdam (In press) . (2001)
[Publications] Fujiwara K,Mochida S: "Etiology and pathophysiology of fulminant hepatic failure. In : Molecular Biology and Immunology for the Treatment of Intractable Liver Diseases"Tsuji T, et al. (eds), Elsevier Science, Amsterdam (In press). (2001)

2000 Fiscal Year Annual Research Report

心停止者肝を肝移植ドナー・ソースとする方法の開発

Principal Investigator

藤原 研司 埼玉医科大学, 医学部, 教授 (80101088)

Research Products

[Publications] Osada N,Mochida S,Inao M,Mashimo Y,Fujiwara K.: "Apoptisis in dissociation between DNA synthesis and cellular functions of activated hepatic stellate cells : A study with carbon tetrachloride-induced rat liver injury."Biochemical Biophysical Research Communication. (In press). (2001)

[Publications] YouSuFu Y,Mochida S,Matsui A,Okamoto H,Fujiwara K.: "TT virus infection in cases of fulminant hepatic failure : Evaluation by clonality based on amino acid sequence of hypervariable regions."Hepatology Research. (In press). (2001)

[Publications] Niimi Y,Mochida S,Matsui A,Inao M,Fujiwara K.: "PKC- and MAPK-independent upregulation of VEGF receptor expressions in human umbilical venous endothelial cells following VEGF stimulation."Hepatology Research. (In press). (2001)

[Publications] Fujiwara K,Mochida S,Matsui A,Nagoshi S.: "Indication and criteria for liver transplantation for fulminant hepatic failure."J Gastroenterology and Hepatology. (In press). (2001)

[Publications] Funyu J,Mochida S,Inao M,Matsui A,Fujiwara K.: "VEGF can act as vascular permeability factor in the hepatic sinusoids through upregulation of porosity of endothelial cells."Biochemical Biophysical Research Communication. 280. 481-485 (2001)

[Publications] Mochida S,Fujiwara K.: "Recent advances in acute and fulminant hepatitis in Japan."Internal Medicine. 40. 175-177 (2001)

[Publications] Mochida S,Fujiwara K.: "Angiogenesis in the liver : A communication system among liver cells through VEGF."Connective Tissue. 32. 389-393 (2000)

[Publications] Ikeda H,Yatomi Y,Yanase M,Satoh H,Maekawa H,Ogata I,Ozaki Y,Takawa Y,Mochida S,Fujiwara K.: "Biological activities of novel lipid mediator sphingosine 1-phosphate in rat hepatic stellate cells."American Journal of Physiology. 279. G304-G310 (2000)

[Publications] Mochida S,Fujiwara.: "Hepatic microcirculation in massive liver necrosis and liver regeneration. In : Gastroenterology and Hepatology : Millennium 2000"Asakura H (eds), Elsevier Science, Amsterdam (In press) . (2001)

[Publications] Fujiwara K,Mochida S: "Etiology and pathophysiology of fulminant hepatic failure. In : Molecular Biology and Immunology for the Treatment of Intractable Liver Diseases"Tsuji T, et al. (eds), Elsevier Science, Amsterdam (In press). (2001)

藤原研司埼玉医科大学, 医学部, 教授 (80101088)