The role of the serum-derived Nanopaticle in the diabetic wound healing disorders

• Project/Area Number: 25462808
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Plastic surgery
• Research Institution: Hyogo Medical University
• Principal Investigator: Kawai Kenichiro 兵庫医科大学, 医学部, 准教授 (80423177)
• Co-Investigator(Kenkyū-buntansha): KAKIBUCHI Masao 兵庫医科大学, 医学部, 教授 (50252664) ; NISHIMOTO Soh 兵庫医科大学, 医学部, 教授 (30281124) ; ISHISE Hisako 兵庫医科大学, 医学部, 病院助手 (30567194) ; FUJITA Kazutoshi 兵庫医科大学, 医学部, 助教 (40461066)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 創傷治癒 / 機械的刺激 / TRPC3 / カルシウムイオンチャネル / カルシウム動態 / イオンチャネル / 血清由来nanoparticle / 血清由来Nanoparticle / 糖尿病 / Adiponectin / Calreticulin

Outline of Final Research Achievements

Initially, we tried to investigate how Adiponectin, which is known to be decreased in diabetic condition, acts on the local Ca2+ homeostasis in the wounds through Serum-derived Nanoparticle formation/degradation. However, it was so difficult to synthesize Adiponectin protein that we started to study about ion channels in the wound simultaneously.
Among Transient Receptor Potential cation channels, TRPC3 was appeared to be up-regulated in the hypertrophic scar contracture tissue. When cyclic stretch stimuli were applied to the cutaneous fibroblasts, the expression of TRPC3 was elevated. Furthermore, in the TRPC3 overexpressing fibroblasts, cyclic stretch stimuli raised cytoplasm Ca2+ concentration , which lead to the phosphorylation of NFκB and the up-regulation of FIbronectin.

Research Products

• [Journal Article] Hypertrophic scar contracture is mediated by the TRPC3 mechanical force transducer via NFkB activation (2015)
  • Author(s): Hisako Ishise, Barrett Larson, Yutaka Hirata, Toshihiro Fujiwara, Soh Nishimoto, Tateki Kubo, Ken Matsuda, Shigeyuki Kanazawa, Yohei Sotsuka, Kazutoshi Fujita, Masao Kakibuchi & Kenichiro Kawai
  • Journal Title: Scientific Reports Volume: 5 Issue: 1 Pages: 11620-11620
  • DOI: 10.1038/srep11620
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] 皮膚創傷治癒過程における血清由来Nanoparticle の役割 (2013)
  • Author(s): 河合建一郎 Barrett J. Larson
  • Journal Title: 兵庫医科大学医学会雑誌 Volume: 38 Pages: 77-82
  • Peer Reviewed
• [Presentation] TRPCチャネルと創傷治癒 (2015)
  • Author(s): 河合建一郎, 石瀬久子, 西本聡, 藤原敏宏, 曽束洋平, 藤田和敏, 外岡真紀, 垣淵正男
  • Organizer: 第24回日本形成外科学会基礎学術集会
  • Place of Presentation: 岩手県民会館 （ 岩手・盛岡市）
  • Year and Date: 2015-10-08
• [Presentation] 皮膚創部における酸化ストレスとTRPCチャネルの関係 (2015)
  • Author(s): 河合建一郎, 石瀬久子, 西本聡, 藤原敏宏, 曽束洋平, 藤田和敏, 外岡真紀, 齋藤拓也, 垣淵正男
  • Organizer: 第7回日本創傷外科学会総会
  • Place of Presentation: 東京ドームホテル （ 東京・文京区）
  • Year and Date: 2015-07-24
• [Presentation] CALCIUM ENTRY VIA TRPC3 CHANNELS TRANSDUCE MECHANICAL FORCE AND ACCERELATE WOUND CONTRACTION (2015)
  • Author(s): Kenichiro Kawai, Hisako Ishise, Barrett Larson, Soh Nishimoto, Toshihiro Fujiwara, Masao Kakibuchi
  • Organizer: The 60th Plastic Surgery Research Council
  • Place of Presentation: Seattle, Washington USA
  • Year and Date: 2015-05-14 – 2015-05-16
• [Presentation] TRPC3 CHANNELS REGULATE EXPRESSION OFFIBRONECTIN VIA NFκB SIGNLING IN RESPONSE TO CYCLIC STRAIN AND CONTRIBUTE TO HYPERTROPHIC SCAR FORMATION (2015)
  • Author(s): Hisako Ishise, Kenichiro Kawai, Barrett Larson, Soh Nishimoto, Toshihiro Fujiwara, Masao Kakibuchi
  • Organizer: The 60th Plastic Surgery Research Council
  • Place of Presentation: Seattle, Washington USA
  • Year and Date: 2015-05-14 – 2015-05-16
• [Presentation] Calcium Entry Via TRPC3 Channels Transduce Mechanical Force And Accerelate Wound Contraction (2015)
  • Author(s): Kenichiro Kawai, Hisako Ishise, Barrett Larson, Soh Nishimoto, Toshihiro Fujiwara, Masao Kakibuchi
  • Organizer: Plastic Surgery Research Council 60th Annual Meeting
  • Place of Presentation: Seattle (USA)
  • Year and Date: 2015-05-14
  • Int'l Joint Research
• [Presentation] TRPC3 Channels Regulate Expression of Fibronectin Via NFκB Signling In Response to Cyclic Strain And Contribute to Hypertrophic Scar Formation (2015)
  • Author(s): Kenichiro Kawai, Hisako Ishise, Barrett Larson, Soh Nishimoto, Toshihiro Fujiwara, Masao Kakibuchi
  • Organizer: Plastic Surgery Research Council 60th Annual Meeting
  • Place of Presentation: Seattle (USA)
  • Year and Date: 2015-05-14
  • Int'l Joint Research
• [Presentation] 細胞力覚チャネルTRPC3が創収縮に果たす役割について (2014)
  • Author(s): 河合建一郎、石瀬久子、藤田和敏、曽束洋平、藤原敏宏、西本聡、垣淵正男
  • Organizer: 第23回日本形成外科学会基礎学術集会
  • Place of Presentation: 長野県松本市
  • Year and Date: 2014-10-09 – 2014-10-10
• [Presentation] 機械的刺激応答チャネルとしてのTRPC3の役割ーFibronectin発現制御機構についてー (2014)
  • Author(s): 石瀬久子、河合建一郎、藤田和敏、曽束洋平、藤原敏宏、西本聡、垣淵正男
  • Organizer: 第23回日本形成外科学会基礎学術集会
  • Place of Presentation: 長野県松本市
  • Year and Date: 2014-10-09 – 2014-10-10
• [Presentation] 創収縮におけるTRPC3の役割について (2014)
  • Author(s): 河合建一郎、石瀬久子、西本聡、藤原敏宏、曽束洋平、藤田和敏、木下将人、齋藤拓也、大島遙、垣淵正男
  • Organizer: 第6回日本創傷外科学会総会・学術集会
  • Place of Presentation: 香川県高松市
  • Year and Date: 2014-07-24 – 2014-07-25
• [Presentation] Serum derived nanoparticles increase the rate of cataneous wound closure (2013)
  • Author(s): Kenichiro Kawai, Barrett Larson, Hisako Ishise, Antoine L. Carré, Soh Nishimoto, Michael T. Longaker, H Peter Lorenz, Masao Kakibuchi.
  • Organizer: The 22nd China-Japan Joint Congress on Plastic Surgery
  • Place of Presentation: Dalian, China