Adiponectin action through regulation of exosome production
| Project/Area Number |
19K08978
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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 |
KITA Shunbun 大阪大学, 医学系研究科, 寄附講座講師 (10746572)
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| Co-Investigator(Kenkyū-buntansha) |
前田 法一 大阪大学, 医学系研究科, 寄附講座准教授 (30506308)
西澤 均 大阪大学, 医学系研究科, 講師 (20379259)
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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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)
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| Keywords | アディポネクチン / エクソソーム / 間葉系幹細胞 / β細胞増殖 / 心不全 / カドヘリン / 糖尿病 / 癌免疫療法 / 幹細胞 / セラミド |
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| Outline of Research at the Start |
脂肪由来分泌因子アディポネクチンが細胞膜アンカー型受容体T-カドヘリンを介して、エクソソームと呼ばれる細胞外微粒子の生合成・分泌を促進することを見出した。本申請では、①アディポネクチンのエクソソーム産生促進を介する臓器保護機序を解明し、②T-カドヘリンの制御機構、及び血中遊離T-カドヘリンの病態生理学的意義を解明する。また、③これらの幹細胞機能における役割を明らかにする。
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| Outline of Final Research Achievements |
Adiponectin is a good protein secreted from fat and is a factor that protects us from various lifestyle-related diseases. Until now, it has been thought that a receptor called AdipoR plays a role, but in fact, we demonstrated that it functions by binding to a special membrane protein called T-cadherin, entering cells, and producing particles called exosomes. This function is also important for stem cell therapies and may be applied to the treatment of severe heart failure and immune checkpoint inhibitor-associated type 1 diabetes. We also found that T-cadherin is released from cells and is also present in the blood, increasing in a diabetic state and helping the growth of insulin-producing cells in the pancreas.
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| Academic Significance and Societal Importance of the Research Achievements |
脂肪から産生される善玉タンパクであるアディポネクチンの働き方を正しく理解することで、再生医療の中でも重要な幹細胞医療にも応用できる方法が見つかってきました。アディポネクチンは肥満で減少してしまうので、肥満は生活習慣病のもとになるだけでなく、幹細胞移植治療の効果も弱らせてしまう恐れがあります。幹細胞治療法は重症心不全に加えて、癌の免疫療法で稀に起こる1型糖尿病にも効果を発揮する可能性を見出しました。また、私たちの発見で、インスリン産生細胞が増えるメカニズムの理解が深まりました。インスリン産生細胞を増やすことが出来れば、多くの糖尿病患者の根本的な治療法につながります。
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Report
(4 results)
Research Products
(52 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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[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
ロート製薬株式会社、国立大学法人大阪大学
Industrial Property Rights Type
特許
Industrial Property Number
2021-026666
Filing Date
2021
Related Report
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