2000 Fiscal Year Final Research Report Summary
PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL SIGNIFICANCE OF ACTIVATION of FIBVRINOLYTIC CASCADE BY AIRWAY TRYPSIN-LIKE PROTEASE
| Project/Area Number |
11670580
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | THE UNIVERSITY OF TOKUSHIMA |
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Principal Investigator |
YASUOKA Susumu THE UNIVERSITY OF TOKUSHIMA, DEPARTMENT OF NURSINNG PROFESSOR, 医療技術短期大学部, 教授 (30035414)
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| Co-Investigator(Kenkyū-buntansha) |
SANO Toshiaki THE UNIVERSITY OF TOKUSHIMA, SCHOOL OF MEDICINE PROFESSOR, 医学部, 教授 (80154128)
NAKAMURA Yoichi THE UNIVERSITY OF TOKUSHIMA, HOSPITAL OF SCHOOL OF MEDICINE LECTURER, 医学部・附属病院, 講師 (00237447)
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| Project Period (FY) |
1999 – 2000
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| Keywords | HUMAN AIRWAY TRYPSIN-LIKE PROTEASE / AIRWAY / CILIATED EPITHELIAL CELLS / FIBRINOLYTIC CASCADE / PROUROKI NASE / FIBRINOGEM / FIBROBLAST / TGF-β1 |
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| Research Abstract |
THIS STUDY WAS UNDERTAKEN TO CLARIFY MECHANISM OF ACTIVATION OF FIBRINOLYTIC CASCADE BY HUMAN AIRWAY TRYPSIN-LIKE PROTEASE(HAT), WHICH WE FOUND IN THE HUMAN AIRWAY, AND TO CLARIFY PATHOPHYSIOLOGICAL SIGNIFICACE OF THIS ACTIVATION.FOLLOWING RESULTS WERE OBTAINED.
1. LOCALIZATION OF HAT IN AIRWAYS : LOCALIZATION OF HAT IN THE AIRWAYS WAS IMMUNOHISTOCHEMICALLY EXAMINED USING FRESH BRONCHIAL TISSUES OBTAINED AT SURGERY.IT WAS SHOWN THAT POSITIVE REACTION WAS FOUND IN BRONCHIAL CILIATED EPITHELIAL CELLS.THIS RESULT INDICATES THAT HAT IS BIOSYNTHESIZED IN AIRWAY EPITHELIAL CELLS.
2. ABILITY TO HYDROLYZE ENDOGENOUS PROTEINS OF HAT : IT WAS SHOWN BY SDS-POLYACRYLAMIDE GEL ELECTROPHORESIS THAT HAT CLEAVES FIBRINIGEN, ESPECIALLY ITS α -CHAIN, AND FIBRIN, BUT DOES NOT PLASMONIGEN ITSELF, AND THAT HAT CONVERTS PROUROKINASE INTO UROKINASE BY LIMITED PROTEOLYSIS.
3. EFFECT OF HAT ON GROWTH AND FUNCTION OF LUNG AND BRONCHIAL FIBROBLASTS : IT WAS SHOWN IN VITRO SYSTEM THAT HAT ENHANCES GROWTH OF BOTH LUNG AND BRONCHIAL FIBROBLASTS, AND IT ALSO ENHANCES PRODUCTION OF TGF-β1 BY BOTH THE FIBROBLASTS.
4. CONCLUSION : IT IS POSTULATED THAT HAT IS BIOSYNTHESIZED IN AIRWAY EPITHELIAL CELLS, AND IS THOUGHT TO BE RELATED TO ACTIVATION OF FIBRINOLYTIC CASCADE BY ACTIVATION OF PROUROKINASE IN THE AIRWAY.IT IS ALSO POSTULATED THAT HAT IS RELATED TO AMPLIFICATION OF REMODELING OF AIRWAY TISSUES IN CRONIC INFLAMATORY DISEASES, BY ACTIVATION OF FIBRINOLYTIC CASCADE, AND BY ENHANCEMENT OF GROWTH AND FUNCTION OF FIBROBLASTS.
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