Role of chymase on development and progression of organ damage induced by metabolic syndrome

• Project/Area Number: 15K08251
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Osaka Medical College
• Principal Investigator: TAKAI Shinji 大阪医科大学, 医学研究科, 教授 (80288703)
• Co-Investigator(Renkei-kenkyūsha): KIN Tokunan 大阪医科大学, 大学院医学研究科, 講師 (90319533)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: キマーゼ / メタボリックシンドローム / 合併症 / 阻害薬 / 高血圧 / NASH / 糖尿病 / 高脂血症 / 脂質異常症 / 脂肪肝 / 非アルコール性脂肪性肝炎

Outline of Final Research Achievements

A novel non-alcoholic steatohepatitis (NASH) model was developed to clarify the role of chymase on metabolic syndrome-derived NASH in spontaneously hypertensive rats fed a high-fat and high-cholesterol diet. In the NASH model, hepatic chymase level was significantly increased, but chymase inhibitor attenuated the development and progression of NASH, resulted in a significant increase of survival rate. A novel hamster metabolic syndrome-derived NASH model was also developed in hamsters fed a high-fat and high-cholesterol diet. In this model, a significant increase of hepatic chymase was also observed.
Chymase played an important role in the development and progression of metabolic syndrome-derived 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 as a Novel Therapeutic Agent for Non-alcoholic Steatohepatitis. (2018)
  • Author(s): Takai S, Jin D.
  • Journal Title: Front Pharmacol Volume: 9 Pages: 144-144
  • DOI: 10.3389/fphar.2018.00144
  • Peer Reviewed / Open Access
• [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
• [Journal Article] Improvement of cardiovascular remodelling by chymase inhibitor (2016)
  • Author(s): Takai S, Jin D.
  • Journal Title: Clin Exp Pharmacol Physiol Volume: 43 Issue: 4 Pages: 387-393
  • DOI: 10.1111/1440-1681.12549
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Recombinant human soluble thrombomodulin improved lipopolysaccharide/d-galactosamine-induced acute liver failure in mice (2015)
  • Author(s): Osumi W, Jin D, Imai Y, Tashiro K, Li ZL, Otsuki Y, Maemura K, Komeda K, Hirokawa F, Hayashi M, Takai S, Uchiyama K.
  • Journal Title: J Pharmacol Sci Volume: 129 Issue: 4 Pages: 233-239
  • DOI: 10.1016/j.jphs.2015.11.007
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 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 Y, Jin D, Tashiro K, Komeda K, Masubuchi S, Hirokawa F, Hayashi M, Takai S, Uchiyama K.
  • Organizer: Digestive Disease Week 2017
  • Int'l Joint Research
• [Presentation] 非アルコール性脂肪性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、髙井真司、内山和久
  • Organizer: 第130回日本薬理学会近畿部会
  • Place of Presentation: 京都大学百周年時計台記念館（京都府京都市）
  • Year and Date: 2016-11-19
• [Presentation] 非アルコール性脂肪性肝炎におけるキマーゼ阻害薬の重要性 (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、髙井真司、内山和久
  • Organizer: 第21回日本病態プロテアーゼ学会 2016年8月5-6日
  • Place of Presentation: 千里ライフサイエンスセンター（大阪府吹田市）
  • Year and Date: 2016-08-05
• [Presentation] 2.Effect of recombinant human soluble thrombomodulin in lipopolysaccharide/D-galactosamine-induced acute liver failure in mice (2016)
  • Author(s): Osumi W, Jin D, Imai Y, Miyaoka Y, Tashiro K, Komeda K ,Hirokawa F, Hayashi M, Takai S, Nishiguchi K, Uchiyama K.
  • Organizer: Digestive Disease Week 2016
  • Place of Presentation: サンディエゴ（米国）
  • Year and Date: 2016-05-22
  • Int'l Joint Research