Proposal of novel concept, Exosome cargo as a novel DAMPs delivery system

• Project/Area Number: 15K15667
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Emergency medicine
• Research Institution: Kagoshima University
• Principal Investigator: MARUYAMA Ikuro 鹿児島大学, 医歯学総合研究科, 特任教授 (20082282)
• Co-Investigator(Kenkyū-buntansha): YAMAKUCHI Munekazu 鹿児島大学, 医歯学域医学系, 准教授 (20325814) ; ITO Takashi 鹿児島大学, 医歯学総合研究科, 講師 (20381171)
• Co-Investigator(Renkei-kenkyūsha): HARADA Yoichiro 鹿児島大学, 医歯学総合研究科, 特任准教授 (80464147)
• Project Period (FY): 2015-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: エクソソーム / DAMPs / PAMPs / HMGB1 / Histones / microRNA / 糖鎖構造 / Heat shock protein / Alix / メラノーマ細胞株A375

Outline of Final Research Achievements

We have been investigating in damage associated molecular patterns, DAMPs, focusing on HMGB1 and histones. We established the specific ELISA assay method and showed that these two DAMPs are worthy of diagnostic marker for DIC and septic shock. Therefore we have stated to establish “exosomal DAMPs”. After the ultracentirifugation of conditioned medium from melanoma, we obtained exosome. The immunoblotting study, the exosome expressed and showed molecules of CD63, CD 81, both are markers of exosome. We also detected high mannose glucose chain. We could positive band for histones, suggesting that exosome contains histones. In conclusion of this preliminary study, DAMP; histones are actually contained into exosome. Whether the exosomal histones exert their cytotoxic effect is remained as a next study. In conclusion we partially succeeded in showing that exosome actually contains DAMP: histones. We are going to study on the cytotoxic bioactivity of this exosomal histones.

Research Products

• [Journal Article] Potential diagnostic markers for disseminated intravascular coagulation of sepsis (2016)
  • Author(s): Toshiaki Iba, Takashi Ito, Ikuro Maruyama, Bernd Jilma, Thorsten Brenner, Marcella C.A. Muller, Nicole P. Juffermans, Jecko Thachil
  • Journal Title: Blood Reviews Volume: 30 Issue: 2 Pages: 149-155
  • DOI: 10.1016/j.blre.2015.10.002
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The E3 ligase synoviolin controls body weight and mitochondrial biogenesis through negative regulation of PGC-1β. (2015)
  • Author(s): Fujita H, Yagishita N, Aratani S, Saito-Fujita T, Morota S, Yamano Y, Hansson MJ, Inazu M, Kokuba H, Sudo K, Sato E, Kawahara K, Nakajima F, Hasegawa D, Higuchi I, Sato T, Araya N, Usui C, Nishioka K, Nakatani Y, Maruyama I, Usui M, Hara N, Uchino H, Elmer E, Nishioka K, Nakajima T.
  • Journal Title: EMBO J. Volume: 34 Issue: 8 Pages: 1042-55
  • DOI: 10.15252/embj.201489897
  • Peer Reviewed / Open Access
• [Journal Article] Gene transfer of high-mobility group box 1 box-A domain in a rat acute liver failure model (2015)
  • Author(s): Tanaka, M
  • Journal Title: Journal of Surgical Research Volume: 194 Issue: 2 Pages: 571-580
  • DOI: 10.1016/j.jss.2014.11.022
  • Peer Reviewed / Open Access