The exploration of exosome involvement in skeletal abnormalities induced by dysregulation of zinc homeostasis
| Project/Area Number |
18K09540
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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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| Review Section |
Basic Section 57020:Oral pathobiological science-related
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| Research Institution | Showa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
川嶋 章弘 昭和大学, 医学部, 講師 (10783376)
田中 準一 昭和大学, 歯学部, 講師 (40710166)
美島 健二 昭和大学, 歯学部, 教授 (50275343)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 骨格形成 / 軟骨 / 細胞・組織 / 遺伝子 / 骨格成長 / 亜鉛トランスポーター / エキソソーム / シグナル伝達 |
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| Outline of Final Research Achievements |
Abnormal zinc metabolism leads to skeletal and immune abnormalities. The purpose of this research project was to elucidate the pathogenesis of skeletal abnormalities caused by disruption of zinc homeostasis. ZIP10 (zinc transporter) deficient cells, which are responsible for intracellular regulation of zinc, showed higher variation in bone metabolism-related gene clusters and gene clusters related to vesicles and exosomes compared to wild-type cells. Isolated exosomes expressed mesenchymal cell-specific markers in addition to known exosome markers, and DIA proteome analysis identified 1798 proteins involved in the developmental process in isolated exosomes of ZIP10-deficient cells. Zinc may regulate bone metabolism-related cell differentiation via exosomes.
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| Academic Significance and Societal Importance of the Research Achievements |
必須微量因子である亜鉛の代謝異常は骨格異常や骨粗鬆症、さらに免疫力の低下をきたし、老化に関わる事が示唆されている。亜鉛の細胞内濃度は亜鉛トランスポーターを介して調節される。本研究課題は、ZIP10欠損マウスを作製し、亜鉛欠乏した骨関連細胞で発現する遺伝子をRNA-sequence法を用いて網羅的に解析した。さらに、細胞からエキソソームを回収し、LC-MS/MSを用いてエキソソームに含まれるタンパク質の解析を行った。亜鉛のエキソソームに対する作用の解明は、報告が少なく、本研究課題の成果は、骨格形成のみならず、関節疾患の病態メカニズムや治療法開発に新たな知見と理解をもたらすと考えられる。
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Report
(5 results)
Research Products
(16 results)
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[Journal Article] Generation of orthotopically functional salivary gland from embryonic stem cells2018
Author(s)
Tanaka Junichi、Ogawa Miho、Hojo Hironori、Kawashima Yusuke、Mabuchi Yo、Hata Kenji、Nakamura Shiro、Yasuhara Rika、Takamatsu Koki、Irie Tarou、Fukada Toshiyuki、Sakai Takayoshi、Inoue Tomio、Nishimura Riko、Ohara Osamu、Saito Ichiro、Ohba Shinsuke、Tsuji Takashi、Mishima Kenji
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Journal Title
Nature Communications
Volume: 9
Issue: 1
Pages: 4216-4216
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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