Novel therapeutic approaches of intestinal stenosis focused on myofibroblasts

• Project/Area Number: 22790677
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Fukuoka University
• Principal Investigator: KURAHARA Lin (HAI Lin) 福岡大学, 医学部, 講師 (00341438)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 下部消化管学(小腸、大腸) / 組織線維化 / 炎症性腸疾患 / 線維化狭窄 / 筋線維芽細胞 / TRPC4 / TRPC6 / カルシウム / TGF-β1 / TGFβ1 / コラーゲン / TNFα / PGE2 / 腸管狭窄 / TRPC1 / Ca^<2+> / NF-κB / 線維化

Research Abstract

TRPC4 and C6 channels may play non-trivial roles in myofibroblast transformation/differentiation, thereby promoting fibrogenesis in the colon. Our results also suggested that myfibroblast signaling pathways regulating interleukin production, which seem associated with the phosphorylation of Smad2, Erk1/2, and p38 MAPK as well as TRPC6-mediated Ca2+ influx. TRPC4 and TRPC6 could be a promising target in treating fibrotic and inflammatory bowel diseases.

Research Products

• [Journal Article] Critical role of TRPC1-mediated Ca2+ entry in decidualization of human endometrial stromal cells (2012)
  • Author(s): Yasuhiro Kawarabayashi, Lin Hai, Akira Honda, Shinji Horiuchi, Hiroshi Tsujioka, Jun Ichikawa, Ryuji Inoue
  • Journal Title: Molecular Endocrinology Volume: 26(5) Issue: 5 Pages: 846-858
  • DOI: 10.1210/me.2011-1259
  • Peer Reviewed
• [Journal Article] Counteracting effect of TRPC1-associated Ca^<2+> influx on TNFα-induced COX-2-dependent prostaglandin E_2 production in human colonic myofibroblasts (2011)
  • Author(s): Hai L, Kawarabayashi Y, Imai Y, Honda A, Inoue R.
  • Journal Title: American Journal of Physiology-Gastrointestinal and Liver Physiology Volume: 301(2) Issue: 2 Pages: G356-G367
  • DOI: 10.1152/ajpgi.00354.2010
  • Peer Reviewed
• [Journal Article] Counteracting effect of TRPC 1-asscoiated Ca^<2+> influx on TNF α induced COX-2-dependent prostaglandin E_2 production in human colonic myofibroblasts (2011)
  • Author(s): Lin Hai, Yasuhiro Kawarabayashi, Yuko Imai, Akira Honda, Ryuji Inoue
  • Journal Title: AMERICAN JOURNAL OF PHYSIOLOGY -GASTROINTESTINAL AND LIVER PHYSIOLOGY Volume: (掲載確定)
  • Peer Reviewed
• [Presentation] Intestinal myofibroblast TRPC4, C6 channels confer fibrogenic potential for human stenosis (2013)
  • Author(s): Lin-Hai Kurahara, Miho Sumiyoshi, Ryuji Inoue
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: 東京
  • Year and Date: 2013-03-29
• [Presentation] Involvement of TRPC6 channel in TGF β 1/SMAD/MAPK/PI3K signaling in human intestinal myofibroblast (2013)
  • Author(s): Miho Sumiyoshi, Rin Kurahara, Ryuji Inoue
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: 東京
  • Year and Date: 2013-03-29
• [Presentation] Involvement of TRPC6 channel in fibrogenic stenosis in human intestinal myofibroblast (2013)
  • Author(s): Lin-Hai Kurahara, Miho Sumiyoshi, Ryuji Inoue
  • Organizer: 第86回日本薬理学会大会
  • Place of Presentation: 福岡
  • Year and Date: 2013-03-22
• [Presentation] Involvement of TRPC6 channel in TGFβ1/SMAD/MAPK/PI3K signaling in human intestinal myofibroblast (2013)
  • Author(s): Miho Sumiyoshi, Lin-Hai Kurahara,Ryuji Inoue
  • Organizer: 第90回日本生理学会大会
  • Place of Presentation: 東京
• [Presentation] Involvement of TRPC channel in fibrogenic stenosis and inflammation in human colonic myofibroblast (2013)
  • Author(s): Lin-Hai Kurahara, Miho Sumiyoshi, Ryuji Inoue
  • Organizer: 第37回国際生理学会（IUPS）
  • Place of Presentation: イギリス・バーミンガム
• [Presentation] 線維化促進因子 TGF-β1 下流に おける消化管筋線維芽細胞 TRPC4,C6 チャネ ルの役割 (2012)
  • Author(s): Lin-Hai Kurahara, Miho Sumiyoshi, Ryuji Inoue
  • Organizer: 第63回西日本生理学会
  • Place of Presentation: 大分
  • Year and Date: 2012-10-19
• [Presentation] 炎症性腸疾患線維化狭窄にお ける消化管筋線維芽細胞 TRPC4,C6 チャネル の役割 (2012)
  • Author(s): Lin-Hai Kurahara, Miho Sumiyoshi, Ryuji Inoue
  • Organizer: 第54回日本平滑筋学会総会
  • Place of Presentation: 東京
  • Year and Date: 2012-08-03
• [Presentation] ヒト子宮内膜間質細胞の脱落膜化過程におけるTRPC1の役割 (2012)
  • Author(s): 瓦林靖広、倉原(海)琳、本田啓、市川純、井上隆司
  • Organizer: 第8回TRP研究会
  • Place of Presentation: 岡崎
  • Year and Date: 2012-06-15
• [Presentation] Intestinal myofibroblast TRPC channels confer fibrogenetic potential for human stenosis (2012)
  • Author(s): Lin-Hai Kurahara, Ryuji Inoue
  • Organizer: 第89回日本生理学会大会
  • Place of Presentation: 松本
  • Year and Date: 2012-03-29
• [Presentation] Counteracting effect of TRPC1 mediated store-operated Ca2+ influx on TNFα-induced COX-2-dependent prostaglandin E2 production in human colonic myofibroblasts (2012)
  • Author(s): Lin-Hai Kurahara, Yasuhiro Kawarabayashi, Akira Honda, Ryuji Inoue
  • Organizer: 第10回日韓シンポジウム
  • Place of Presentation: 韓国慶州
  • Year and Date: 2012-02-18
• [Presentation] Counteracting effect of TRPC1 mediated store-operated Ca^<2+> influx on TNFα-induced COX-2-dependent prostaglandin E_2 production in human colonic myofibroblasts (2012)
  • Author(s): Lin-Hai Kurahara, Yasuhiro Kawarabayashi, Akira Honda, Ryuji Inoue
  • Organizer: 第10回日韓シンポジウム
  • Place of Presentation: 韓国慶州
  • Year and Date: 2012-02-18
• [Presentation] 炎症性腸疾患線維化狭窄における消化管筋線維芽細胞TRPC4,C6チャネルの役割 (2012)
  • Author(s): 倉原（海）琳、住吉美保、井上隆司
  • Organizer: 第54回日本平滑筋学会総会
  • Place of Presentation: 東京
• [Presentation] 線維化促進因子TGF-β1下流における消化管筋線維芽細胞TRPC4,C6チャネルの役割 (2012)
  • Author(s): Lin-Hai Kurahara, Miho Sumiyoshi, Ryuji Inoue
  • Organizer: 第63回西日本生理学会
  • Place of Presentation: 大分
• [Presentation] ヒト子宮内膜間質細胞の脱落膜化過程におけるTRPC1の役割 (2012)
  • Author(s): 瓦林靖広、倉原（海）琳、本田啓、市川純、井上隆司
  • Organizer: 第8回 TRP研究会
  • Place of Presentation: 岡崎
• [Presentation] 腸管狭窄線維化の進行における消化管筋線維芽細胞 TRP チャネルの役割 (2011)
  • Author(s): Hai Lin, Ryuji Inoue
  • Organizer: 第62回西日本生理学 会
  • Place of Presentation: 佐賀
  • Year and Date: 2011-10-14
• [Presentation] 腸管狭窄線維化の進行における消化管筋線維芽細胞TRPチャネルの役割 (2011)
  • Author(s): Lin Kurahara, Ryuji Inoue
  • Organizer: 第62回西日本生理学会
  • Place of Presentation: 佐賀
  • Year and Date: 2011-10-14
• [Presentation] 消化管筋線維芽細胞におけるTRPC1/SOC/NF-κB シグナル伝達を介した COX-2 発現の制御 (2010)
  • Author(s): Hai Lin, Yasuhiro Kawarabayashi, Akira Honda, Ryuji Inoue
  • Organizer: 第87回日本生理学会大会・シンポジウム
  • Place of Presentation: 盛岡
  • Year and Date: 2010-05-21
• [Presentation] シンポジウム「ストア作動性カルシウム流入活性化機構とその生理的役割」消化管筋線維芽細胞におけるTRPC1/SOC/NF-κBシグナル伝達を介したCOX-2発現の制御 (2010)
  • Author(s): 倉原琳
  • Organizer: 第87回日本生理学会大会
  • Place of Presentation: 盛岡
  • Year and Date: 2010-05-21