Cross talk analysis of biological clock and autophagy in wound tissue

• Project/Area Number: 15K15264
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Legal medicine
• Research Institution: Wakayama Medical University
• Principal Investigator: Kondo Toshikazu 和歌山県立医科大学, 医学部, 教授 (70251923)
• Co-Investigator(Kenkyū-buntansha): 野坂 みずほ 和歌山県立医科大学, 医学部, 助教 (00244731) ; 石田 裕子 和歌山県立医科大学, 医学部, 講師 (10364077) ; 木村 章彦 和歌山県立医科大学, 医学部, 准教授 (60136611)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: autophagy / 体内時計 / 創傷治癒 / 損傷の生活反応 / 法医診断 / オートファジー / 損傷診断

Outline of Final Research Achievements

We found that autophagy was quickly suppressed in the skin wound tissue after infliction, which might be a useful marker for wound vitality in the forensic practice. Conversely, we found that Rev-erb-alpha and ROR-gamma of clock genes markedly increased at the protein level in the wound tissue. Since suppression of autophagy by treatment with 3-Methyladenine increased ROR-gamma, autophagy suppression seemed to induce an increase of ROR-gamma protein in the wound tissue.
These changes in the wound tissue revealed that they act on Keap 1/Nrf 2 system and induce the expression of antioxidant genes, thereby contributing to promotion of wound healing.

Research Products

• [Journal Article] Autophagy in skin wounds: a novel marker for vital reactions (2015)
  • Author(s): Kimura A, Ishida Y, Nosaka M, Shiraki M, Hama M, Kawaguchi T, Kuninaka Y, Shimada E, Yamamoto H, Takayasu T, Kondo T.
  • Journal Title: Int J Legal Med Volume: - Issue: 3 Pages: 537-541
  • DOI: 10.1007/s00414-015-1168-4
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 皮膚創傷治癒におけるAkt/autophagy axisとKeap1/Nfr2相互作用の役割 (2016)
  • Author(s): 木村章彦
  • Organizer: 第46回日本創傷治癒学会
  • Place of Presentation: 東京
  • Year and Date: 2016-12-09
• [Presentation] 皮膚創傷治癒におけるautophagyの役割 (2015)
  • Author(s): 19.木村章彦
  • Organizer: 第45回日本創傷治癒学会
  • Place of Presentation: 東京
  • Year and Date: 2015-11-30