Molecular mechanism of adipose tissue inflammation through Mincle and cell-cell interactions

• Project/Area Number: 15K09423
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Nagoya University
• Principal Investigator: Tanaka Miyako 名古屋大学, 環境医学研究所, 助教 (60622793)
• Co-Investigator(Renkei-kenkyūsha): YAMASAKI Sho 大阪大学, 微生物病研究所, 教授 (40312946) ; Uezumi Akiyoshi 地方独立行政法人東京都健康長寿医療センター, 東京都健康長寿医療センター研究所, 専門副部長 (60434594) ; Ogawa Yoshihiro 九州大学, 大学院医学研究院, 教授 (70291424)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: マクロファージ / 脂肪組織線維化 / 内因性リガンド / Mincle / 肥満 / 異所性脂肪 / 病原体センサー

Outline of Final Research Achievements

I developed a new animal model of adipose tissue fibrosis instead of high fat diet-induced obese model, which takes at least 4 months for adipose tissue fibrosis. Applying an ischemia-reperfusion model to the adipose tissue, I could establish the new model, which takes only 2 weeks for adipose tissue fibrosis involved in the upregulation of Mincle gene expression and CLS (crown-like structure) formation. I also identified the adipose tissue fibroblasts using high fat diet-induced obese mice that express GFP under collagen promoter. I found that the GFP-positive cells in epididymal fat tissue are almost all positive for PDGFRα. In addition, the character of PDGFRα-positive cells in epididymal fat tissue is different from that in subcutaneous fat tissue and more active type of fibroblasts.

Research Products

• [Journal Article] Synthetic “smart gel” provides glucose-responsive insulin delivery in diabetic mice (2017)
  • Author(s): Matsumoto Akira、Tanaka Miyako、Matsumoto Hiroko、Ochi Kozue、Moro-oka Yuki、Kuwata Hirohito、Yamada Hironori、Shirakawa Ibuki、Miyazawa Taiki、Ishii Hitoshi、Kataoka Kazunori、Ogawa Yoshihiro、Miyahara Yuji、Suganami Takayoshi
  • Journal Title: Sci. Adv. Volume: 3 Issue: 11 Pages: 0723-0723
  • DOI: 10.1126/sciadv.aaq0723
  • Peer Reviewed / Open Access
• [Journal Article] Molecular mechanism of obesity-induced ‘metabolic’ tissue remodeling (2017)
  • Author(s): Tanaka Miyako、Itoh Michiko、Ogawa Yoshihiro、Suganami Takayoshi
  • Journal Title: J. Diabetes Investig. Volume: 9 Issue: 2 Pages: 256-261
  • DOI: 10.1111/jdi.12769
  • Peer Reviewed / Open Access
• [Journal Article] WNK4 is an Adipogenic Factor and Its Deletion Reduces Diet-Induced Obesity in Mice. (2017)
  • Author(s): Takahashi D, Mori T, Sohara E, Tanaka M, Chiga M, Inoue Y, Nomura N, Zeniya M, Ochi H, Takeda S, Suganami T, Rai T, Uchida S.
  • Journal Title: EBioMedicine Volume: 18 Pages: 118-27
  • DOI: 10.1016/j.ebiom.2017.03.011
  • Peer Reviewed / Open Access
• [Journal Article] Antifibrotic effect of pirfenidone in a mouse model of human nonalcoholic steatohepatitis. (2017)
  • Author(s): C. Komiya, M. Tanaka, K. Tsuchiya, N. Shimazu, K. Mori, S. Furuke, Y. Miyachi, K. Shiba, S. Yamaguchi, K. Ikeda, K. Ochi, K. Nakabayashi, K. Hata, M. Itoh, T. Suganami, Y. Ogawa.
  • Journal Title: Sci. Rep. Volume: 7 Issue: 1 Pages: 44754-44754
  • DOI: 10.1038/srep44754
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Inflammatory responses increase secretion of MD-1 protein (2016)
  • Author(s): Thomas Jennings R, Odkhuu E, Nakashima A, Morita N, Kobayashi T, Yamai I, Tanaka M, Suganami T, Haga S, Ozaki M, Watanabe Y, Nagai Y, Takatsu K, Kikuchi-Ueda T, Ichimonji I, Ogawa Y, Takagi H, Yamazaki T, Miyake K, Akashi-Takamura S
  • Journal Title: International Immunology Volume: 28 Issue: 10 Pages: 503-512
  • DOI: 10.1093/intimm/dxw031
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The H3K9 methyltransferase Setdb1 regulates TLR4-mediated inflammatory responses in macrophages. (2016)
  • Author(s): R. Hachiya, T. Shiihashi, I. Shirakawa, Y. Iwasaki, Y. Matsumura, Y. Oishi, Y. Nakayama, Y. Miyamoto, I. Manabe, K. Ochi, M. Tanaka, N. Goda, J. Sakai, T. Suganami, Y. Ogawa.
  • Journal Title: Sci. Rep. Volume: 6 Issue: 1 Pages: 28845-28845
  • DOI: 10.1038/srep28845
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Isoliquiritigenin attenuates adipose tissue inflammation in vitro and adipose tissue fibrosis through inhibition of innate immune responses in mice. (2016)
  • Author(s): Watanabe Y, Nagai Y, Honda H, Okamoto N, Yamamoto S, Hamashima T, Ishii Y, Tanaka M, Suganami T, Sasahara M, Miyake, K, Takatsu K.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 23097-23097
  • DOI: 10.1038/srep23097
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Mincle, macrophage-inducible C-type lectin, plays an important role in the pathogenesis of renal ischemia-reperfusion injury (2018)
  • Author(s): Miyako Tanaka, Marie Saka-Tanaka, Kozue Ochi, Kumiko Fujieda, Hiro Kohda, Naotake Tsuboi, Shoichi Maruyama, Yoshihiro Ogawa, Takayoshi Suganami
  • Organizer: 2018 Keystone Symposia for the meeting on The Resolution of Inflammation in Health and Disease
  • Int'l Joint Research
• [Presentation] グルコース応答性ゲルを用いた自律的インスリンデバイスの開発 (2017)
  • Author(s): 田中 都，桒田博仁，越智 梢，松本裕子，白川伊吹，宮原裕二，石井 均，小川佳宏，松元 亮，菅波孝祥
  • Organizer: 第38回日本肥満学会学術大会
• [Presentation] イムノメタボリズムと脂肪組織炎症 (2016)
  • Author(s): 田中 都，越智梢，菅波孝祥，小川佳宏
  • Organizer: 第37回日本肥満学会
  • Place of Presentation: 東京
  • Year and Date: 2016-10-07
  • Invited
• [Presentation] メタボリックシンドロームと脂肪組織機能破綻 (2016)
  • Author(s): 田中 都，越智梢，菅波孝祥，小川佳宏
  • Organizer: 第89回日本内分泌学会学術総会
  • Place of Presentation: 京都
  • Year and Date: 2016-04-21
  • Invited
• [Presentation] Mincle, a novel pathogen sensor in macrophages, underlies obesity-induced adipose tissue fibrosis in mice (2016)
  • Author(s): Miyako Tanaka, Kozue Ochi, Yoshihiro Ogawa, Takayoshi Suganami
  • Organizer: 2016 Keystone Symposia for the meeting on Fibrosis: From Basic Mechanisms to Targeted Therapies
  • Place of Presentation: Keystone, Colorado, USA
  • Year and Date: 2016-02-07
  • Int'l Joint Research
• [Presentation] 生体の脂質代謝異常とアディポサイトカイン (2015)
  • Author(s): 田中 都，菅波孝祥，小川佳宏
  • Organizer: 第23回日本心血管内分泌代謝学会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-10
  • Invited
• [Presentation] メタボリックシンドロームにおける脂肪組織炎症・線維化の意義と分子機構解明 (2015)
  • Author(s): 田中 都，菅波孝祥，小川佳宏
  • Organizer: 第59回日本薬学会関東支部大会
  • Place of Presentation: 千葉
  • Year and Date: 2015-09-12
  • Invited
• [Presentation] 肥満脂肪組織の線維化分子機構について (2015)
  • Author(s): 田中 都，菅波孝祥，小川佳宏
  • Organizer: 第58回日本糖尿病学会年次学術集会
  • Place of Presentation: 山口
  • Year and Date: 2015-05-21
  • Invited
• [Book] Chronic Inflammation Mechanisms and Regulation (2016)
  • Author(s): T. Suganami, M. Tanaka, and Y. Ogawa.
  • Total Pages: 679
  • Publisher: Springer Open
• [Book] Innovative Medicine Basic Research and Development (2015)
  • Author(s): Y. Ogawa , T. Suganami , M. Itoh ,M. Tanaka.
  • Total Pages: 330
  • Publisher: Springer Open