Establishment of novel biomarkers to prevent the development of CKD complicated with obesity and diabetes targeting monocytic function.
| Project/Area Number |
16K08959
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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 |
Laboratory medicine
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| Research Institution | Department of Clinical Research, National Hospital Organization Kyoto Medical Center |
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Principal Investigator |
Yamakage Hajime 独立行政法人国立病院機構(京都医療センター臨床研究センター), 糖尿病研究部, 研究員 (40598900)
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| Co-Investigator(Kenkyū-buntansha) |
小谷 和彦 自治医科大学, 医学部, 教授 (60335510)
浅原 哲子 (佐藤哲子) 独立行政法人国立病院機構(京都医療センター臨床研究センター), 内分泌代謝高血圧研究部, 研究部長 (80373512)
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| Research Collaborator |
Suganami Takayoshi
Yahata Kensei
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
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)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 単球機能 / 肥満 / 糖尿病 / 慢性腎臓病 / TREM2 / バイオマーカー / 予防 / 単球 / 炎症 / 脳心腎合併症 / 病態検査学 / 臨床検査医学 |
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| Outline of Final Research Achievements |
We identified a novel obesity-/diabetes-susceptibile gene, triggering receptor expressed on myeloid cells 2 (TREM2), which is mainly expressed on monocytes and microglia.
Our cohort study based on obesity and diabetes has shown that serum TREM2 may be a novel biomarker for cognitive decline. At present, the long-term follow-up is being conducted to elucidate the pathophysiological significance of TREM2 in chronic kidney disease (CKD). We further generated TREM2-deficient mice and found that TREM2 is involved in diabetes, obesity and insulin resistance. We are planning to investigate the implications of monocyte function and TREM2 in the functionally linked decline of the brain, heart and kidney.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、単球由来ミクログリアやマクロファージに発現する細胞表面蛋白質：TREM2はインスリン抵抗性の増悪や脂肪組織の慢性炎症、さらには腎障害に関連する可能性が示唆された。今後、脳・心臓・腎臓の連動的な炎症亢進・機能低下に対する、単球・MφのM1/M2極性やTREM2の関連性を明らかにすることで、新たな治療法の開発などへの展開が期待できる。
生活習慣病・CVD/CKDの急増が危惧される中、本研究にてヒト単球・Mφ機能を標的とした新規早期診断・治療法が新たに構築されれば、健康寿命の延伸、高齢化社会のQOL改善、ひいては医療費抑制にも貢献でき、社会的意義が大きいと期待される。
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Report
(4 results)
Research Products
(56 results)
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[Journal Article] Prediction of functional profiles of gut microbiota from 16S rRNA metagenomic data provides a more robust evaluation of gut dysbiosis occurring in Japanese type 2 diabetic patients2017
Author(s)
Inoue R, Ohue-Kitano R, Tsukahara T, Tanaka M, Masuda S, Inoue T, Yamakage H, Kusakabe T, Hasegawa K, Shimatsu A, Satoh-Asahara N
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Journal Title
Journal of Clinical Biochemistry and Nutrition
Volume: 61
Issue: 3
Pages: 217-221
DOI
NAID
ISSN
0912-0009, 1880-5086
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Peer Reviewed / Open Access
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[Journal Article] Omega-3 polyunsaturated fatty acids suppress the inflammatory responses of lipopolysaccharide-stimulated mouse microglia by activating SIRT1 pathways.2017
Author(s)
Inoue T, Tanaka M, Masuda S, Ohue-Kitano R, Yamakage H, Muranaka K, Wada H, Kusakabe T, Shimatsu A, Hasegawa K, Satoh-Asahara N
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Journal Title
Biochim Biophys Acta
Volume: 1862
Issue: 5
Pages: 552-560
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Effect of statins on atherogenic serum amyloid A and α1-antitrypsin low-density lipoprotein complexes.2016
Author(s)
4)Miyazaki Y, Katanasaka Y, Sunagawa Y, Hirano-Sunagawa S, Funamoto M, Morimoto E, Komiyama M, Shimatsu A, Satoh-Asahara N, Yamakage H, Wada H, Hasegawa K, Morimoto T
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Journal Title
Int J Cardiol
Volume: 225
Pages: 332-336
DOI
Related Report
Peer Reviewed
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[Journal Article] Highly absorptive curcumin reduces serum atherosclerotic low-density lipoprotein levels in patients with mild COPD.2016
Author(s)
Funamoto M, Sunagawa Y, Katanasaka Y, Miyazaki Y, Imaizumi A, Kakeya H, Yamakage H, Satoh-Asahara N, Komiyama M, Wada H, Hasegawa K, Morimoto T
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Journal Title
Int J Chron Obstruct Pulmon Dis
Volume: 11
Pages: 2029-2034
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Hyperglycemia and Inflammatory Property of Circulating Monocytes are Associated with Inflammatory Property of Carotid Plaques in Patients Undergoing Carotid Endarterectomy.2016
Author(s)
Tanaka M, Masuda S, Matsuo Y, Sasaki Y, Yamakage H, Muranaka K, Wada H, Hasegawa K, Tsukahara T, Shimatsu A, Satoh-Asahara N
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Journal Title
J Atheroscler Thromb
Volume: 23
Pages: 1212-1221
NAID
Related Report
Peer Reviewed / Open Access
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[Presentation] 肥満・糖尿病における新規認知症予知指標・TREM2の病態意義 ―国立病院機構多施設共同研究―2018
Author(s)
浅原哲子, 田中将志, 山陰一, 井上隆之, 北野隆司, 村中和哉, 荒木里香, 的場ゆか, 齋藤美穂, 栗田征一郎, 米澤一也, 田中剛史, 鈴木雅裕, 澤村守夫, 西村元伸, 小鳥真司, 日下部徹, 島津章
Organizer
第91回日本内分泌学会学術集会
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[Presentation] Novel Mechanisms to Suppress Systemic Chronic Inflammation by the Gut Microbiota-derived Heat Shock Protein through Regulation of Intestinal Immunity.2016
Author(s)
Kitano R, Hashimoto K, Nakamoto M, Furukawa Y, Hoshizawa N, Maeda H, Masuda T, Kitabatake N, Tanaka M, Masuda S, Inoue T, Yamakage H, Muranaka K, Shimatsu A, Tani F, Satoh-Asahara N
Organizer
第21回アディポサイエンスシンポジウム
Place of Presentation
大阪
Related Report
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