Mechanisms of Chymase on the Non-alcoholic steatohepatitis

• Project/Area Number: 26860176
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: Osaka Medical College
• Principal Investigator: Tashiro Keitaro 大阪医科大学, 医学部, 講師 (20645527)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: キマーゼ / NASH / 非アルコール性脂肪肝炎 / SHRSP5/Dmcrラット / HFC食 / Chymase / TGF-β / MMP-9 / メカニズム / キマーゼ阻害薬 / 脂肪肝炎 / 肝線維化

Outline of Final Research Achievements

The effect of the chymase inhibitor TY-51469 on the development and progression of non-alcoholic steatohepatitis (NASH) was evaluated in rats fed a high-fat and high-cholesterol (HFC) diet. To evaluate the preventive effect of TY-51469 on the development of NASH, stroke-prone spontaneously hypertensive rat 5 (SHRSP5)/Dmcr rats were fed either a normal or HFC diet for 8 weeks, and concurrently administered either placebo or TY-51469. Eight weeks after HFC diet, significant increases of steatosis, fibrosis and chymase-positive cells were observed in liver from the placebo-treated rats. Significant increases of myeloperoxidase, transforming growth factor-b, matrix metalloproteinase-9, and collagen I mRNA levels were also observed. However, all parameters were significantly attenuated in the TY-51469-treated group. Chymase inhibitor may be applicable to preventing the development and progression of NASH.

Research Products

• [Journal Article] A novel hamster nonalcoholic steatohepatitis model induced by a high-fat and high-cholesterol diet (2018)
  • Author(s): Miyaoka Y, Jin D, Tashiro K, Masubuchi S, Ozeki M, Hirokawa F, Hayashi M, Takai S, Uchiyama K.
  • Journal Title: Experimental Animals Volume: 67 Issue: 2 Pages: 239-247
  • DOI: 10.1538/expanim.17-0126
  • NAID: 130006733605
  • ISSN: 0007-5124, 1341-1357, 1881-7122
  • Peer Reviewed
• [Journal Article] Chymase inhibitor prevents the development and progression of?non-alcoholic steatohepatitis in rats fed a high-fat and high-cholesterol diet (2017)
  • Author(s): Miyaoka Yuta、Jin Denan、Tashiro Keitaro、Komeda Koji、Masubuchi Shinsuke、Hirokawa Fumitoshi、Hayashi Michihiro、Takai Shinji、Uchiyama Kazuhisa
  • Journal Title: Journal of Pharmacological Sciences Volume: 134 Issue: 3 Pages: 139-146
  • DOI: 10.1016/j.jphs.2017.04.005
  • Peer Reviewed / Open Access
• [Presentation] chymase inhibitor prevents the development and progression of non-alcoholic steatohepatitis in rats (2017)
  • Author(s): Miyaoka, Yuta; JIn, Denan; Tashiro, Keitaro; Komeda, koji; Masubuchi, Shinsuke; Hirokawa, Fumitoshi; Hayashi, Michihiro; Takai, Shinji; Uchiyama, Kazuhisa
  • Organizer: DDW2017
  • Int'l Joint Research
• [Presentation] 非アルコール性脂肪肝炎におけるキマーゼ阻害薬の重要性 (2016)
  • Author(s): 宮岡雄太、 田代圭太郎、米田浩二、廣川文鋭、金徳男、林道廣、高井真司、内山和久
  • Organizer: 日本病態プロテアーゼ学会
  • Place of Presentation: 千里ライフサイエンスセンター
• [Presentation] 非アルコール性脂肪肝炎に対するキマーゼ阻害薬の有用性 (2016)
  • Author(s): 宮岡雄太、金徳男、田代圭太郎、米田浩二、廣川文鋭、林道廣
  • Organizer: 第130回日本薬理学会近畿部会
  • Place of Presentation: 京都