| Project/Area Number |
08557001
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
General anatomy (including Histology/Embryology)
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| Research Institution | AKITA UNIVERSITY |
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Principal Investigator |
SENOO Haruki AKITA UNIVERSITY SCHOOL OF MEDICINE,2ND DEPARTMENT OF ANATOMY,PROFESSOR, 医学部, 教授 (90171355)
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| Co-Investigator(Kenkyū-buntansha) |
HATA Ryuichiro TOKYO MEDICAL AND DENTAL UNIVERSITY,MEDICAL RESEARCH INSTITUTE,DEPARTMENT OF TIS, 難治疾患研究所, 助教授 (10014276)
IMAI Katsuyuki AKITA UNIVERSITY SCHOOL OF MEDICINE,2ND DEPARTMENT OF ANATOMY,ASSISTANT RESEARCH, 医学部, 助手 (80006741)
SATO Mitsuru AKITA UNIVERSITY SCHOOL OF MEDICINE,2ND DEPARTMENT OF ANATOMY,ASSISTANT RESEARCH, 医学部, 助手 (60226008)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥6,400,000 (Direct Cost: ¥6,400,000)
Fiscal Year 1997: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1996: ¥3,400,000 (Direct Cost: ¥3,400,000)
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| Keywords | artificial liver / three-dimensional structure / L-ascorbic acid 2-phosphate / hepatic stellate cells / hepatic parenchymal cells / collagen / extracellular matrix / integrin / 細胞外マトリックス / 人工肝臓(三次元) / ビタミンC / ビタミンA肝蔵細胞 |
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| Research Abstract |
We established the procedure for isolation of hepatic stellate cells (vitamin A-storing cells) and parenchymal cells by perfusion of collagenase through the hepatic portal vein of rat. These cells were cultured in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum or William's medium E.Isolated rat stellate cells and human hepatoma HepG2 cells contacted directly and formed a three-dimensional structure when co-cultured in the medium supplemented with a long-acting vitamin C derivative (L-ascorbic acid 2-phosphate ; Asc 2-P). Expression and three-dimensional distribution of phosphorylated proteins in HepG2 cells changed dramatically by contact with the stellate cells.
Asc 2-P regulates cellular functions through promotion of the production of extracellular matrix. A kind and three-dimensional structure of extracellular matrix was found to regulate reversibly morphology, proliferation, and functions of the stellate cells. A peptide DGEA and integrin alpha2beta1 was essential for the direct adhesion of the stellate cells and type I collagen. Our present study demonstrated that signals from integrin stimulated phosphorylation of tyrosine and phosphatidylinositol, assembly of microtubules and fibrillar actin, and regulation of the morphology of the stellate cells. The native form of type I collagen which production is stimulated by Asc 2-P was important for the regulation of morphology and function of the hepatic stellate cells. The data obtained in our present study will promote the development of the three-dimensional artificial liver.
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