Renal protective role of adiponectin and clinical significance of circulating T-cadherin concentration
| Project/Area Number |
19K08980
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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 54040:Metabolism and endocrinology-related
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| Research Institution | Osaka University |
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Principal Investigator |
MAEDA Norikazu 大阪大学, 医学系研究科, 寄附講座准教授 (30506308)
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| Co-Investigator(Kenkyū-buntansha) |
西澤 均 大阪大学, 医学系研究科, 講師 (20379259)
喜多 俊文 大阪大学, 医学系研究科, 寄附講座講師 (10746572)
藤島 裕也 大阪大学, 医学系研究科, 助教 (10779789)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | アディポネクチン / T-カドヘリン / 慢性腎臓病 / メタボリックシンドローム / 糖尿病 |
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| Outline of Research at the Start |
心血管イベント発症基盤としての慢性腎臓病（CKD）が注目されている。肥満や糖尿病に起因するCKD患者は増加の一途を辿っており、腎機能低下・腎不全を未然に防ぐ事が重要である。肥満・糖尿病で低下する脂肪細胞特異的分泌蛋白アディポネクチン（APN）は、T-カドヘリン（T-cad）を介して血管に集積し、抗動脈硬化作用を発揮することを申請者は明らかにしてきた。
しかし、CKD発症・進展におけるAPN/T-cadの役割は未だ明らかでは無い。本研究では、APN/T-cadシステムによる腎保護作用を明らかにし、糖尿病やCKDとAPN/T-cadシステムの臨床的意義を明らかにしたい。
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| Outline of Final Research Achievements |
We generated and analyzed a renal ischemia and reperfusion model in mice lacking adiponectin or T-cadherin. Our study clearly showed that adiponectin/T-cadherin system played a significant role in maintenance for vascular barrier function and homeostasis of vascular pericytes. Furthermore, we established ELISA system to measure soluble T-cadherin in bloodstream and demonstrated the existence of three forms of soluble T-cadherin (130-kDa, 100-kDa, and 30-kDa). Soluble T-cadherin concentrations were significantly correlated with various clinical parameters, suggesting that soluble T-cadherin is a novel biomarker.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、アディポネクチン/T-カドヘリンシステムは腎保護作用を有しており、慢性腎臓病や糖尿病腎症の予防・治療に応用できる可能性を示した。また、可溶性T-カドヘリンを測定することで、糖尿病や心疾患の新たなバイオマーカーとしての応用が期待される。
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Report
(4 results)
Research Products
(31 results)
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[Journal Article] Identification and clinical associations of three forms of circulating T-cadherin in human serum.2021
Author(s)
Fukuda S, Kita S, Miyashita K, Iioka M, Murai J, Nakamura T, Nishizawa H, Fujishima Y, Morinaga J, Oike Y, Maeda N, Shimomura I.
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Journal Title
J Clin Endocrinol Metab.
Volume: -
Issue: 5
Pages: 1333-1344
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Plasma xanthine oxidoreductase activity in Japanese patients with type 2 diabetes across hospitalized treatment.2021
Author(s)
Kawachi Y, Fujishima Y, Nishizawa H, Nagao H, Nakamura T, Akari S, Murase T, Taya N, Omori K, Miyake A, Fukuda S, Takahara M, Kita S, Katakami N, Maeda N, Shimomura I.
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Journal Title
J Diabetes Investig.
Volume: -
Issue: 8
Pages: 1512-1520
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Increased vascular permeability and severe renal tubular damage after ischemia-reperfusion injury in mice lacking adiponectin or T-cadherin.2021
Author(s)
Tsugawa-Shimizu Y, Fujishima Y, Kita S, Minami S, Sakaue TA, Nakamura Y, Okita T, Kawachi Y, Fukuda S, Namba-Hamano T, Takabatake Y, Isaka Y, Nishizawa H, Ranscht B, Maeda N, Shimomura I.
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Journal Title
Am J Physiol Endocrinol Metab.
Volume: 320
Issue: 2
Pages: E179-E190
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Adiponectin Stimulates Exosome Release to Enhance Mesenchymal Stem-Cell-Driven Therapy of Heart Failure in Mice.2020
Author(s)
Nakamura Y, Kita S, Tanaka Y, Fukuda S, Obata Y, Okita T, Nishida H, Takahashi Y, Kawachi Y, Tsugawa-Shimizu Y, Fujishima Y, Nishizawa H, Takakura Y, Miyagawa S, Sawa Y, Maeda N, Shimomura I.
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Journal Title
Mol Ther.
Volume: 28
Issue: 10
Pages: 2203-2219
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Renal Function is Associated with Blood Neurofilament Light Chain Level in Older Adults2020
Author(s)
Akamine S, Marutani N, Kanayama D, Gotoh S, Maruyama R, Yanagida K, Sakagami Y, Mori K, Adachi H, Kozawa J, Maeda N, Otsuki M, Matsuoka T, Iwahashi H, Shimomura I, Ikeda M, Kudo T
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Journal Title
Scientific Reports
Volume: 10
Issue: 1
Pages: 20350-20350
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Native adiponectin in serum binds to cells expressing T-cadherin, but not AdipoRs or calreticulin2020
Author(s)
Shunbun Kita, Shiro Fukuda, Yuto Nakamura, Yoshinari Obata, Yoshimitsu Tanaka, Tomonori Okita, Shigeki Masuda, Yuri Shimizu, Yusuke Kawachi, Emi Horitani, Takaaki Sakaue, Yuya Fujishima, Hitoshi Nishizawa, Norikazu Maeda, and Iichiro Shimomura
Organizer
Keystone Symposia, Diabetes: Glucose Control and Beyond
Related Report
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[Presentation] Action mechanism of high-molecular weight multimer adiponectin - possible role of stem cells, T-cadherin, and exosomes for organ protections2020
Author(s)
Yuto Nakamura, Shunbun Kita, Yoshinari Obata, Shiro Fukuda, Yoshimitsu Tanaka, Yuya Fujishima, Hitoshi Nishizawa, Norikazu Maeda, and Iichiro Shimomura
Organizer
Keystone Symposia, Diabetes: Glucose Control and Beyond
Related Report
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