| Co-Investigator(Kenkyū-buntansha) |
KOKAI Yasuo Sapporo Medical University School of Medicine, Department of Pathology Assistant, 医学部, 講師 (20178239)
OYAMADA Masahito Kyoto Prefectural University of Mdicine Department of Pathology Assistant Profes, 医学部, 講師 (30183255)
SAWADA Norimasa Sapporo Medical University School of Medicine, Department of Pathology Associate, 医学部, 助教授 (30154149)
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| Research Abstract |
We developed the 7H6 monoclonal antibody, which preferentially reacts with a novel tight junction-associated protein (7H6 antigen). The expression of this protein at tight junctions was shown to correlate with the paracellular barrier function of various epithelial cells. In this project, we isolated a series of cDNA clones encoding 7H6-reactive polypeptides, and found that the RL5.3 clone encods the first rodent counterpart of molecular the motor protein essential for the chromosome seggregation in yeast, xenopus and chicken cells.
We tested the effects of bacterial endotoxin (LPS) on the barrier function of intestinal mucosa, and found that LPS abolishes intestinal barrier function in association with the disappearance of 7H6 antigen from the cell border, when LPS was applied to the basolateral surface of intestinal cells.
We examined the expression and intracellular localization of 7H6 antigen, occludin, and ZO-1 during the course of cholestasis following bile duct ligation, and found that 7H6 antigen dispersed from the bile canalicular membrane cholestasis developes, whereas the expression of other two tight junction proteins was upregulated.
It was strongly suggested that the 7H6 antigen may act as a molecular motor at tight junctions and its dislocation is crucial for the pathogenesis of enteropathy and cholostasis.
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