| Project/Area Number |
14571093
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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 |
Metabolomics
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
YOKODE Masayuki KYOTO UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, DEPARTMENT OF CLINICAL INNOVATIVE MEDICINE, PROFESSOR, 医学研究科, 教授 (20252447)
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| Co-Investigator(Kenkyū-buntansha) |
ARAI Hidenori KYOTO UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, DEPARTMENT OF GERIATRIC MEDICINE, ASSOCIATE PROFESSOR, 医学研究科, 講師 (60232021)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | SMOOTH MUSCLE CELLS / MACROPHAGES / ENDOTHELIAL CELLS / BONE MARROW / VASCULAR PROGENITOR CELLS / RECEPTOR TYROCINE KINASE / VASCULAR INJURY / REMODELING / 骨髄幹細胞 / ノックアウトマウス / PDGF / MCS-F / 増殖因子 / サイトカイン |
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| Research Abstract |
WE HAVE LOMG BEEN INTERESTED IN SIGNAL PATHWAYS VIA RECEPTOR TYROSINE KINASES IN VASCULAR BIOLOGY, AND HAVE ENERGETICALLY CONTINUED TO ANALYZE VASCULAR TISSUE FORMATION/REMODELING REACTION IN VIVO BY ADMINISTRATION OF FUNCTIONALLY BLOCKING ANTIBODIES TO MODEL ANIMALS. DURING THIS TERM OF PROJECT, WE FOCUSED ON GLOMERULAR DEVELOPMENT FROM THE NEOVASCULARIZATION POINT OF VIEW, AND DISCOVERED THAT ANTI-PDGF RECEPTOR β ANTIBODY RESULTS IN APOPTOSIS OF GLOMERULAR ENDOTHELIA AND INHIBITION OF GLOMERULAR FORMATION IN NEONATAL MICE, WHICH MAY BE MEDIATED BY MESANGIAL CELLS AND PERICYTES.
NEXT, IN ORDER TO EXAMINE THE BEHAVIOR OF BONE MARROW (BM)-DERIVED PROGENITOR CELLS IN VASCULAR REMODELING, WE UTILIZED A CUFF-INDUCED VASCULAR INJURY MODEL AFTER TRANSPLANTATION OF THE BM FROM GREEN FLUORESCENT PROTEIN (GFP)TRANSGENIC MICE. WE FOUND THAT MOST OF THE MACROPHAGES RECRUITED IN SITU WERE GFP-POSITIVE, AND SOME OF THE SMOOTH MUSCLE CELLS (SMCS) AND ENDOTHELIAL CELLS WERE ALSO GFP-POSITIVE. ADMINISTRATION OF AN ANTI-c-fms ANTIBODY RESULTED IN A MARKED DECREASE IN MACROPHAGES AND A RELATIVE INCREASE OF SMCS, WHILE ADMINISTRATION OF ANTIBODIES AGAINST THE PDGF RECEPTOR β CAUSED A PROMINENT DECREASE IN SMCS AND A RELATIVE INCREASE IN MACROPHAGES. THIS STUDY INDICATES THAT BMDERIVED CELLS PLAY AN IMPORTANT ROLE IN VASCULAR REMODELING, AND THAT DIFFERENTIATION OF MACROPHAGES AND SMCS MIGHT BE DEPENDENT ON EACH OTHER.
FURTHERMORE, FOR THE PURPOSE OF INVESTIGATING ATHEROSCLEROSIS AS AN IMMUNOLOGICAL REACTION, WE PROVIDED A LARGE AMMOUNT OF INTACT HUMAN IMMUNOGROBULIN TO APOLIPOPROTEIN EDEFICIENT MICE FED BY HIGH-FAT DIET, AND FOUND INHIBITION OF ATHEROGENESIS AND MACROPHAGE RECRUITMENT IN THE AORTIC ROOTS. SINCE THE EFFECT WAS NOT SEEN WITH AN ADMINISTRATION OF F(ab')_2, WE CONCLUDE THAT IMMUNOGLOBULIN SUPPRESSES ATHEROSCLEROSIS VIA Fc PORTION AND CYTOTOXIC T LYMPHOCYTES.
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