1994 Fiscal Year Final Research Report Summary
Molecular Pathology of Hepatocyte cytoskeleton
| Project/Area Number |
04404031
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
MORI Michio Sapporo Medical University School of Medicine, Professor, 医学部, 教授 (00045288)
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| Co-Investigator(Kenkyū-buntansha) |
OYAMADA Yumiko Sapporo Medical University School of Medicine, Instructor, 医学部, 助手 (40231245)
OYAMADA Masahito Sapporo Medical University School of Medicine, Instructor, 医学部, 助手 (30183255)
HATTORI Atsuo Sapporo Medical University School of Medicine, Instructor, 医学部, 助手 (90208538)
SAWADA Norimasa Sapporo Medical University School of Medicine, Associate Professor, 医学部, 講師 (30154149)
ENOMOTO Katsuhiko Sapporo Medical University School of Medicine, Assistant Professor, 医学部, 助教授 (20151988)
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| Project Period (FY) |
1992 – 1994
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| Keywords | Cytoskeleton / Molecular pathology / Tight junction / Barrier function / Inhibition of metastasis / Liver disease / Bile canalicular contraction / Hepatocarcinogenesis |
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| Research Abstract |
1. Roles of the cytoskeleton for the meintenance of hepatocyte functions were studied in isolated hepatocytos by confocal laser scanning microscopy and time-lapse videomicroscopy in combination with immunostaining, microinjection, and fluorescent Ca -indicator treatment.
We have found that even under serum-free conditions the bile cansliclus shows periodical contraction based on pericanalichlar actin-microfilaments. Frequency of the contraction was increased by the treatment with endothelin-1 in a dose-dependent manner up to 2nM.A transient increase in the concentration of intracellular Ca was induced upon the addtion of endothelin-1 to the medeum. By usint isolated rat cardiac myocytes we found that synchronized contruction of a cluster of myocytes occurrs in association with the development of gap junctional communication between cardiac myocytes, suggesting that elevated intracytoplasmic Ca is transferred into the neighboring cells and triggers the contraction.
2. We have generated a novel monoclanal antibody 7H6 which specifically recognizes a 155kD tight junction protein (7H6 antigen) which associates with the cytoskeletal element localized preferentially underneath the tight junction membrane. We found that the expression of 7H6 antigen at tight junctions enhances paracellular barrier function of endothelial and epithelial cells. Since impaired paracellular barrier of vascular endothelial cells induces leakage of plasma proteins and extravasation of inflammatory cells, it is important to elucidate the molecular structure of the 7H6 antigen and molecular mechnisms by which the 7H6 antigen regulates the paracellular barrier functio of tight junctios. Extensive further studies are now in progress in our laboratory.
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