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 |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Showa University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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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 / 動脈硬化 / マクロファージ / カルパイン-6 / CWC22 / カルパイン－６ / mRNAスプライシング / ピノサイトーシス |
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| 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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| 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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Report
(4 results)
Research Products
(21 results)
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[Journal Article] Light-at-night exposure affects brain development through pineal allopregnanolone-dependent mechanisms2019
Author(s)
Haraguchi S, Kamata M, Tokita T, Tashiro KI, Sato M, Nozaki M, Okamoto-Katsuyama M, Shimizu I, Han G, Chowdhury VS, Lei XF, Miyazaki T, Kim-Kaneyama JR, Nakamachi T, Matsuda K, Ohtaki H, Tokumoto T, Tachibana T, Miyazaki A, Tsutsui K.
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Journal Title
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] The impact of stromal Hic-5 on the tumorigenesis of colorectal cancer through lysyl oxidase induction and stromal remodeling.2018
Author(s)
Omoto T, Kim-Kaneyama JR, Lei XF, Orimo A, Ohnishi K, Yoshihara K, Miyauchi A, Li S, Gao L, Umemoto T, Tanaka J, Nakahara K, Takeya M, Ishida F, Kudo SE, Haraguchi S, Miyazaki T, Miyazaki A.
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Journal Title
Oncogene.
Volume: 37
Issue: 9
Pages: 1205-1219
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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