Regulatory mechanisms of exosome production by adiponectin and effect of favine on atherosclerosis and thrombus formation.
| Project/Area Number |
18H02863
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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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 |
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| Co-Investigator(Kenkyū-buntansha) |
福原 淳範 大阪大学, 医学系研究科, 寄附講座准教授 (00437328)
喜多 俊文 大阪大学, 医学系研究科, 寄附講座講師 (10746572)
加藤 恒 大阪大学, 医学系研究科, 助教 (20705214)
前田 法一 大阪大学, 医学系研究科, 寄附講座准教授 (30506308)
小林 祥子 大阪大学, 医学系研究科, 助教 (80649111)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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| Keywords | アディポネクチン / エクソソーム / 幹細胞 / セラミド / カドヘリン / Favine / T-カドヘリン / 間葉系幹細胞 / 受容体 / 動脈硬化 / 血栓 |
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| Outline of Final Research Achievements |
We identified T-cadherin, a cell-surface membrane protein, as the specific receptor for native adiponectin. Adiponectin enhances exosome biogenesis and secretion from the cells expressing T-cadherin, and protects the endothelium, renal function, stimulates muscle regeneration. Cell therapy based on mesenchymal stem cells needs circulating adiponectin to secrete exosomes and exert therapeutic functions to heart failure models. T-cadherin circulates also as soluble forms and we developed a new EIA system.
We also uncovered the importance of the Favine-regulated pathway in atherosclerosis.
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| Academic Significance and Societal Importance of the Research Achievements |
アディポネクチンの作用はこれまでアディポRという膜タンパクを介するAMPKの活性化作用等で説明されてきたが、T-カドヘリンが主要な結合タンパクであり、エクソソーム産生促進によって多様な生理作用が発揮され得ることが分かった。本成果はCOVID-19治療にも応用されつつある間葉系幹細胞治療にも応用できる。
脂肪・血管分泌因子Favineは動脈硬化の予防治療に有用である可能性を示した。
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Report
(4 results)
Research Products
(51 results)
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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] 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] 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] Adiponectin promotes muscle regeneration through binding to T-cadherin.2019
Author(s)
Tanaka Y, Kita S, Nishizawa H, Fukuda S, Fujishima Y, Obata Y, Nagao H, Masuda S, Nakamura Y, Shimizu Y, Mineo R, Natsukawa T, Funahashi T, Ranscht B, Fukada SI, Maeda N, Shimomura I.
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Journal Title
Sci. Rep.
Volume: 9
Issue: 1
Pages: 1-12
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Adiponectin/T-cadherin system enhances exosome biogenesis and decreases cellular ceramides by exosomal release.2018
Author(s)
Obata Y, Kita S, Koyama Y, Fukuda S, Takeda H, Takahashi M, Fujishima Y, Nagao H, Masuda S, Tanaka Y, Nakamura Y, Nishizawa H, Funahashi T, Ranscht B, Izumi Y, Bamba T, Fukusaki E, Hanayama R, Shimada S, Maeda N, Shimomura I.
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Journal Title
JCI Insight
Volume: 3(8)
Issue: 8
Pages: 1-18
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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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
Int'l Joint Research
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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, Obesity and NAFLD: Mechanisms and Therapeutics
Related Report
Int'l Joint Research
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[Patent(Industrial Property Rights)] 糖尿病治療剤2021
Inventor(s)
喜多 俊文、下村 伊一郎、前田 法一、西田 浩之
Industrial Property Rights Holder
喜多 俊文、下村 伊一郎、前田 法一、西田 浩之
Industrial Property Rights Type
特許
Industrial Property Number
2021-026666
Filing Date
2021
Related Report
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