2000 Fiscal Year Annual Research Report

オステオポンチンによる障害肝でのマクロファージ浸潤機構の解明

Research Project

Project/Area Number	11670529
Research Institution	Saitama Medical School
Principal Investigator	持田智埼玉医科大学, 医学部, 助教授 (20219968)
Co-Investigator(Kenkyū-buntansha)	稲生実枝埼玉医科大学, 医学部, 助手 (70286037) 松井淳埼玉医科大学, 医学部, 助手 (40260484)
Keywords	オステオポンチン / 肝マクロファージ / 星細胞 / 肝細胞 / ケモカイン / 肝線維化 / transgenic mice / 広汎肝壊死
Research Abstract	肝におけるosteopontin(Osp)の発現調節機構を検討し,以下の成果が得られた。 1)肝星細胞におけるOspのmRNA及び蛋白発現は,TGF-βの刺激により増強した。一方,IL-6,PDGF,FGF-2などのサイトカインやMCP-1,MIP-1αなどのケモカインはOsp発現に影響を与えなかった。従って,星細胞におけるOsp発現は,Smadを介する細胞内シグナルで調節されていることが明らかになった。 2)従来,肝細胞はOspを発現しないとされてきた。しかし,ヒト慢性肝疾患で免疫組織学的検討を行うと,肝細胞にも染色性が観察された。肝細胞における染色性は,慢性肝疾患の進展度と相関しておた。初代培養肝細胞を用いた検討により,肝細胞におけるOsp発現もTGF-βの刺激で増強することが判明した。 3)高分化肝細胞癌はOspを発現することを見出した。以上より,Ospは広汎肝壊死のみならず,肝線維化や発癌の過程にも影響を与えている可能性がある。そこで,B6マウス由来のオステオポンチンcDNAを肝特異的なhuman serum amyloid P component(hSAP)プロモーターを有する発現ベクター(PLG1-hSAP)に入れたコンストラクトを作成し,これをB6受精卵にマイクロインジェクションすることでトランスジェニックマウスを作成した。F1をB6マウスと掛け合わせて,現在,ヘテロのF2を得ている。今後,更にホモの系を確立し,これを用いて肝壊死,線維化,再生及び発癌の病態連繋を検討する予定である。

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

オステオポンチンによる障害肝でのマクロファージ浸潤機構の解明

Principal Investigator

持田 智 埼玉医科大学, 医学部, 助教授 (20219968)

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)

持田智埼玉医科大学, 医学部, 助教授 (20219968)