Elucidation of unique characteristics of renal fibroblasts in fibrosis
| Project/Area Number |
17K19550
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pathology, Infection/Immunology, and related fields
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2017-06-30 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2018: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2017: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
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| Keywords | 線維化 / 線維芽細胞 / マスト細胞 / コラーゲン / マクロファージ / 慢性炎症 / 腎尿細管間質線維化 / 筋線維芽細胞 / ミエロイド細胞 / 細胞外マトリックス / 慢性腎不全 / ミエロイド系細胞 / 抗線維化抗体 / 慢性腎臓病 / 腎線維化 |
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| Outline of Final Research Achievements |
Excessive accumulation of extracellular matrix such as type I collagen induced fibrosis and eventually causing organ failure. In kidney, renal interstitial fibrosis is a common pathology when chronic kidney disease was aggravated. However, the underlined mechanisms of kidney fibrosis especially interstitial fibrosis have not been well elucidated. We newly found unique myeroid cell populations, which are capable of producing collagen, are increased in the fibrotic kidney. Those myeroid cell populations are induced by fibrogenic renal fibroblasts in vitro. Importantly, those fibrogenic fibroblasts are increased by activation of mast cells. Taken together, the triangular interaction of those cellular populations could be a major pathological event for renal fibrotic disease and considered as a new drug target.
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| Academic Significance and Societal Importance of the Research Achievements |
本課題はこれまで申請者が取り組んできた、生体恒常性維持のための「線維芽細胞―免疫細胞相互作用」についての研究成果から着想を進めた研究課題である。本研究から、コラーゲンを選択的に産生し、線維化促進に働くミエロイド系細胞を見出し、この細胞の誘導プロセスから腎線維芽細胞の特殊性や新たな活性化機序が明らかになった新規性・独自性の高い研究として位置付けられる。
「組織特異的な病原性線維芽細胞による線維化誘導機構」という新しいコンセプトの立証に繋がると考えられ、病原性線維芽細胞を標的とした新規治療につながる成果である。
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Report
(3 results)
Research Products
(19 results)
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[Journal Article] Eosinophil depletion suppresses radiation-induced small intestinal fibrosis.2018
Author(s)
Takemura N, Kurashima Y, Mori Y, Okada K, Ogino T, Osawa H, Matsuno H, Aayam L, Kaneto S, Park EJ, Sato S, Matsunaga K, Tamura Y, Ouchi Y, Kumagai Y, Kobayashi D, Suzuki Y, Yoshioka Y, Nishimura J, Mori M, Ishii KJ, Rothenberg ME, Kiyono H, Akira S, Uematsu S.
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Journal Title
Sci Transl Med.
Volume: --
Issue: 429
Pages: 264-273
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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