Roles of lipid G protein-coupled receptors in the regulation of gastrointestinal inflammation.

• Project/Area Number: 15H06727
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Pharmacology in pharmacy
• Research Institution: Kyoto Pharmaceutical University
• Principal Investigator: Tsukahara Takuya 京都薬科大学, 薬学部, 研究員 (70755925)
• Project Period (FY): 2015-08-28 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: Gタンパク共役型脂質受容体 / 炎症性腸疾患 / GPR35 / GPR40 / 正常消化管上皮細胞 / GLP-2

Outline of Final Research Achievements

GPR35 activation promoted wound repair by colonic epithelial cells, and ameliorated onset of DSS-induced colitis via coupling of Gi protein, decrease in cAMP, upregulation of fibronectin and integrin α5 expression, and ERK phosphorylation in colonic epithelial cells. GPR40 stimulation was effective in both onset and mucosal healing of DSS-induced colitis, mediated by increase in GLP-2 production. Our results indicates that lipid G protein-coupled receptors such as GPR35 and GPR40 may be novel candidates for therapeutic target in inflammatory bowel disease.

Research Products

• [Journal Article] NOX1/NADPH Oxidase Expressed in Colonic Macrophages Contributes to the Pathogenesis of Colonic Inflammation in Trinitrobenzene Sulfonic Acid-Induced Murine Colitis (2017)
  • Author(s): Yokota H, Tsuzuki A, Shimada Y, Imai A, Utsumi D, Tsukahara T, Matsumoto M, Amagase K, Iwata K, Nakamura A, Yabe-Nishimura C, Kato S
  • Journal Title: The Journal of Pharmacology and Experimental Theraｐeutics Volume: 360(1) Issue: 1 Pages: 192-200
  • DOI: 10.1124/jpet.116.235580
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] GPR35シグナルを介した大腸上皮修復促進および大腸炎抑制作用 (2017)
  • Author(s): 橋本奈生子、塚原卓矢、松本健次郎、天ケ瀬紀久子、加藤伸一
  • Organizer: 日本薬学会
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-24
• [Presentation] GPR40活性化によるマウスデキストラン硫酸ナトリウム誘起大腸炎に対する保護的役割 (2017)
  • Author(s): 磯山加奈、塚原卓矢、松本健次郎、天ケ瀬紀久子、加藤伸一
  • Organizer: 日本薬学会
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-24
• [Presentation] 大腸上皮細胞の遊走に対するGタンパク共役型受容体GPR35の役割 (2016)
  • Author(s): 塚原卓矢、内海大知、松本健二郎、天ケ瀬紀久子、加藤伸一
  • Organizer: 日本潰瘍学会
  • Place of Presentation: 旭川
  • Year and Date: 2016-09-02
• [Presentation] G-Protein-Coupled Receptor 35 Contributes to Mucosal Healing in Colonic Epithelial Cells in mice (2016)
  • Author(s): Takuya Tsukahara, Nahla Hamouda, Daichi Utsumi, Kenjiro Matsumoto, Kikuko Amagase, Shinichi Kato
  • Organizer: Digestive Disease Week 2016
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2016-05-21
  • Int'l Joint Research
• [Presentation] G Protein-Coupled Receptor 35 (GPR35) Contributes to Mucosal Healing in Mouse Colonic Epithelial Cells (2016)
  • Author(s): Takuya Tsukahara, Nahla Hamouda, Daichi Utsumi, Kenjiro Matsumoto, Kikuko Amagase and Shinichi Kato
  • Organizer: Digestive Disease Week (DDW) 2016
  • Place of Presentation: San Diego
  • Year and Date: 2016-05-21
  • Int'l Joint Research