Targeting bioactive lipid receptors for drug development

2013 Fiscal Year Final Research Report

• Project/Area Number: 23390061
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Akita University
• Principal Investigator: ISHII Satoshi 秋田大学, 医学(系)研究科(研究院), 教授 (10300815)
• Co-Investigator(Kenkyū-buntansha): OHTO Takayo 秋田大学, 大学院・医学系研究科, 助教 (80511378) ; YASUDA Daisuke 秋田大学, 大学院・医学系研究科, 助教 (70594951)
• Project Period (FY): 2011-04-01 – 2014-03-31
• Keywords: 脂質 / シグナル伝達 / LPA / リゾホスファチジン酸 / LPA4 / 化合物ライブラリー

Research Abstract

Through the analysis of mice deficient in the fourth lysophosphatidic receptor (LPA4), we previously revealed that LPA4 is involved in development of type 2 diabetes. In this study, we found that LPA4 negatively regulates mitochondria biogenesis by activating the Rho/Rho kinase pathway and then suppresses adipogenesis. LPA4 antagonists are expected to promote adipogenesis and may be useful for the treatment of patients with type 2 diabetes. In this study, therefore, we screened LPA4 antagonists from a chemical library.

Research Products

• [Journal Article] TDAG8 activation inhibits osteoclastic bone resorption (2014)
  • Author(s): Hikiji, H., Endo, D., Horie, K., Harayama, T., Akahoshi, N., Igarashi, H., Kihara, Y., Yanagida, K., Takeda, J., Koji, T., Shimizu, T., and Ishii, S
  • Journal Title: FASEB J Volume: 28 Pages: 871-879
  • DOI: 10.1096/fj.13-233106
  • Peer Reviewed
• [Journal Article] Antiobese function of platelet-activating factor : increased adiposity in platelet-activating factor receptor-deficient mice with age (2014)
  • Author(s): Sugatani, J., Sadamitsu, S., Yamaguchi, M., Yamazaki, Y., Higa, R., Hattori, Y., Uchida, T., Ikari, A., Sugiyama, W., Watanabe, T., Ishii, S., Miwa, M., and Shimizu, T
  • Journal Title: FASEB J Volume: 28 Pages: 440-452
  • DOI: 10.1096/fj.13-233262
  • Peer Reviewed
• [Journal Article] Decrease in circulating autotaxin by oral administration of prednisolone (2013)
  • Author(s): Sumida, H., Nakamura, K., Yanagida, K., Asano, Y., Kadono, T., Tamaki, K., Igarashi, K., Aoki, J., Sato, S., Ishii, S., Shimizu, T., and Yatomi, Y
  • Journal Title: Clin. Chim. Acta Volume: 415 Pages: 74-80
  • DOI: 10.1016/j.cca.2012.10.003
  • Peer Reviewed
• [Journal Article] Current progress in non-Edg family LPA receptor research (2013)
  • Author(s): Yanagida, K., Kurikawa, Y., Shimizu, T., and Ishii, S
  • Journal Title: Biochim. Biophys. Acta Volume: 1831 Pages: 33-41
  • DOI: 10.1016/j.bbalip.2012.08.003
  • Peer Reviewed
• [Journal Article] Orally active lysophosphatidic acid receptor antagonist attenuates pancreatic cancer invasion and metastasis in vivo (2012)
  • Author(s): Komachi, M., Sato, K., Tobo, M., Mogi, C., Yamada, T., Ohta, H., Tomura, H., Kimura, T., Im, D.S., Yanagida, K., Ishii, S., Takeyoshi, I., and Okajima F
  • Journal Title: Cancer Sci Volume: 103 Pages: 1099-1104
  • DOI: 10.1111/j.1349-7006.2012.02246.x
  • Peer Reviewed
• [Journal Article] Non-Edg family LPA receptors : the cutting edge of LPA research (2011)
  • Author(s): Yanagida, K. and Ishii, S
  • Journal Title: J. Biochem Volume: 150 Pages: 223-232
  • DOI: 10.1093/jb/mvr087
  • Peer Reviewed
• [Presentation] 骨髄造血幹細胞の維持と分化におけるリゾホスファチジン酸受容体LPA4 の機能解析 (2013)
  • Author(s): 五十嵐秀光, 石井聡
  • Organizer: 第86回日本生化学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2013-09-11
• [Presentation] Roles of lysophosphatidic acid receptor LPA4 in diet-induced obesity and insulin resistance (2013)
  • Author(s): Yanagida, K., Kubota, N., Kadowaki, T., Shimizu, T., and Ishii, S
  • Organizer: FASEB Summer Research Conference/Lysophospholipid and Other Related Mediators -From Bench to Clinic
  • Place of Presentation: Niseko (Japan)
  • Year and Date: 2013-08-06
• [Presentation] 内蔵脂肪型肥満/インスリン抵抗性の進行におけるリゾホスファチジン酸受容体LPA4 の関与 (2013)
  • Author(s): 柳田圭介, 窪田直人, 門脇孝, 清水孝雄, 石井聡
  • Organizer: 第55回脂質生化学会
  • Place of Presentation: 松島
  • Year and Date: 2013-06-07
• [Presentation] Involvement of lysophosphatidic acid receptor LPA4 in chronic inflammation in adipose tissue and insulin resistance caused by diet-induced obesity (2012)
  • Author(s): Yanagida, K., Kubota, N., Kadowaki, T., Shimizu, T., and Ishii, S
  • Organizer: International Endotoxin and Innate Immunity Society Meeting 2012 (IEIIS2012)
  • Place of Presentation: Tokyo (Japan)
  • Year and Date: 2012-10-24
• [Presentation] 脂質メディエーターの多彩な機能 (2011)
  • Author(s): 石井聡, 清水孝雄
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-23
• [Remarks]
  • URL: http://www.med.akita-u.ac.jp/~bougyo/Home.html