Malnutrition delayed wound healing by HMGB1-related prolonged inflammation

• Project/Area Number: 19K10128
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57030:Conservative dentistry-related
• Research Institution: Kobe Tokiwa Junior College (2021); Okayama University (2019-2020)
• Principal Investigator: Yamashiro Keisuke 神戸常盤大学短期大学部, 口腔保健学科, 教授 (30581087)
• Co-Investigator(Kenkyū-buntansha): 青柳 浩明 岡山大学, 歯学部, 客員研究員 (10814501) ; 宝田 剛志 岡山大学, 医歯薬学総合研究科, 教授 (30377428) ; 西堀 正洋 岡山大学, 医歯薬学総合研究科, 特命教授 (50135943)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 歯周病 / 炎症 / 低栄養 / 創傷治癒 / HMGB1 / マクロファージ / 幹細胞

Outline of Research at the Start

本研究の概要は以下である。
1.低栄養時の慢性炎症は，HMGB1 の分泌が継続するために遷延化するのでは?
2.低栄養時の創傷治癒は，HMGB1 分泌量が初期炎症には不十分であり，またその後も分泌が継続するために遅延するのでは?
これらの仮説を検証するために，歯周炎モデルマウスを用いた低栄養時の慢性炎症遷延化のメカニズム解析，および抜歯モデルマウスを用いた低栄養時の創傷治癒遅延のメカニズム解析を行う。

Outline of Final Research Achievements

In Japan, the gap between average life expectancy and healty life expectancy bacomes a big problem. This divergence is caused by diseases such as fractures and lifestyle-related diseases in the elderly. Malnutrition is one of the causes of further exacerbation of these diseases. In this study, we hypothesized that HMGB1, an inflammation mediator, is involved as one of the causes of prolonged inflammation during malnutrition. We made the malnutrition model mice and observed the wound healing process after tooth extraction. The factors related to inflammation (HMGB1 and IL-1β) expression were increasedand the actores related to regeneration and mesenchymal stem cells were decreased in the malnutriotion group compared to the control group. From these results, it was clarified that HMGB1-mediated delayed wound healing occurs in malnutrition.

Academic Significance and Societal Importance of the Research Achievements

高齢者の低栄養はQOL向上の点からも大変重要な課題である。低栄養になると，傷が治癒しにくくなったり，すでに抱えている慢性疾患が悪化したりすることが考えられる。我々はHMGB1という因子が炎症を悪化させるだけでなく，傷が治る際にも重要な働きをすることを明らかとしてきた。本研究において，低栄養時のHMGB1の働きの一部が解明された。今後はHMGB1を検査に用いたり，また低栄養の患者に対して適切な栄養補助を行う際の指標になりうると考えられる。

Research Products

• [Journal Article] Malnutrition delayed wound healing after tooth extraction by HMGB1-related prolonged inflammation (2021)
  • Author(s): Yao Zhang, Hidetaka Ideguchi, Hiroaki Aoyagi, Keisuke Yamashiro, Tadashi Yamamoto, Masahiro Nishibori, Shogo Takashiba
  • Journal Title: Int Immunopharmacol Volume: 96 Pages: 107772-107772
  • DOI: 10.1016/j.intimp.2021.107772
  • Peer Reviewed / Open Access
• [Journal Article] Elucidation of the mechanism of prolonged inflammation and delayed wound healing during malnutrition: possible HMGB1 dysfunction (2021)
  • Author(s): Keisuke Yamashiro
  • Journal Title: Impact Volume: 2021 Issue: 6 Pages: 26-26
  • DOI: 10.21820/23987073.2021.6.26
  • Open Access
• [Journal Article] High Mobility Group Box 1 Expression in Oral Inflammation and Regeneration (2020)
  • Author(s): Keisuke Yamashiro, Hidetaka Ideguchi, Hiroaki Aoyagi, Chiaki Yoshihara-Hirata, Anna Hirai, Risa Suzuki-Kyoshima, Yao Zhang, Hidenori Wake, Masahiro Nishibori, Tadashi Yamamoto, ShogoTakashiba
  • Journal Title: Frontiers in Immunology Volume: 11 Pages: 1461-1461
  • DOI: 10.3389/fimmu.2020.01461
  • NAID: 120006880201
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Delayed Wound Healing after Tooth Extraction under Malnutrition (2020)
  • Author(s): Y. ZHANG, H. IDEGUCHI, H. AOYAGI, K. YAMASHIRO, T. YAMAMOTO, M. NISHIBORI, S. TAKASHIBA
  • Organizer: Japanese Association for Dental Research
  • Int'l Joint Research