2019 Fiscal Year Final Research Report
Establishment of the strategy for treatment of lifestyle-related diseases by targeting macrophage mRNA splicing
Project/Area Number |
17K09869
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Metabolomics
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Research Institution | Showa University |
Principal Investigator |
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Project Period (FY) |
2017-04-01 – 2020-03-31
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Keywords | 創傷治癒 / カルパスタチン / カルパイン / PDGF受容体 |
Outline of Final Research Achievements |
Transformation of fibroblasts to myofibroblasts has a central role in fibrogenic responses in dermal wound healing. Calpastatin, an endogenous inhibitor of calpains, is enriched in pre-existing vessels, but not in newly-formed vessels in mouse wound sites. Overexpression of calpastatin to endothelial cells (ECs) delays wound healing in mice, together with reduction in keratinocyte layer, extracellular matrix deposition, and myofibroblast accumulation. Expression of PDGF-B and PDGF-beta receptor declined by calpastatin transduction. Topical application of PDGF-BB accelerates wound healing in control mice, which was cancelled by calpastatin transduction. Thus, calpain systems in ECs have a key role in PDGF-beta receptor signaling in fibroblasts, EC-driven myofibroblast differentiation and subsequent fibrogenic responses.
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Free Research Field |
生化学
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Academic Significance and Societal Importance of the Research Achievements |
我々は、動脈硬化発症の分子機構を解明する過程で、細胞内カルシウム依存性タンパク質分解酵素であるカルパインが動脈硬化促進因子として作用していることを明らかにしてきた。さらにカルパインの病態生理学的意義を解明する過程で、皮膚の創傷治癒過程においてはカルパインが治癒促進因子として作用していることを本研究で明らかにした。
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