Functional elucidation and therapeutic application of protease in kidney injury by metabolic syndrome

• Project/Area Number: 15K19460
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Kumamoto University
• Principal Investigator: Mizumoto Teruhiko 熊本大学, 医学部附属病院, 特任助教 (80749193)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 尿蛋白 / メタボリックシンドローム / セリンプロテアーゼ / 糸球体障害 / プロテアーゼ / カモスタット / アポトーシス / 上皮細胞 / 糸球体傷害

Outline of Final Research Achievements

Severe proteinuria observed in the High salt group were substantially attenuated by both Camostat and Hydralazine. The reduction levels in BP were comparable, but the anti-proteinuric effect of camostat was much greater than that of Hydralazine. High salt diet induced apoptosis of glomerular epitherial cells through activation of mineralocorticoid receptor. This study suggested that serine protease inhibitor attenuates apoptosis of glomerular epithelial cells and improves urinary protein. Taken together, camostat showed an anti-proteinuric effect by defending podocyte from apoptosis beyond its anti-hypertensive action.

Research Products

• [Journal Article] A serine protease inhibitor attenuates aldosterone-induced kidney injuries via the suppression of plasmin activity. (2016)
  • Author(s): Y. Kakizoe, Y. Miyasato, T. Onoue, T. Nakagawa, M. Hayata, K. Uchimura, J. Morinaga, T. Mizumoto, M. Adachi, T. Miyoshi, Y. Sakai, K. Tomita, M. Mukoyama, K. Kitamura
  • Journal Title: Journal of Pharmacological Sciences Volume: 132 Issue: 2 Pages: 145-153
  • DOI: 10.1016/j.jphs.2016.09.005
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Combination therapy with renin-angiotensin-aldosterone system inhibitor telmisartan and serine protease inhibitor camostat mesilate provides further renoprotection in a rat chronic kidney disease model. (2016)
  • Author(s): Yuki Narita, Miki Ueda, Kohei Uchimura, Yutaka Kakizoe, Yoshikazu Miyasato, Teruhiko Mizumoto, Jun Morinaga, Manabu Hayata, Terumasa Nakagawa, Masataka Adachi, Taku Miyoshi, Yoshiki Sakai, Daisuke Kadowaki, Sumio Hirata, Masashi Mukoyama, Kenichiro Kitamura
  • Journal Title: Journal of Pharmacological Sciences Volume: 130 Issue: 2 Pages: 110-116
  • DOI: 10.1016/j.jphs.2016.01.003
  • Peer Reviewed / Open Access
• [Journal Article] The serine protease inhibitor camostat mesilate attenuates the progression of chronic kidney disease through its antioxidant effects. (2015)
  • Author(s): Miki Ueda, Kohei Uchimura, Yuki Narita, Yoshikazu Miyasato, Teruhiko Mizumoto, Jun Morinaga, Manabu Hayata, Yutaka Kakizoe, Masataka Adachi, Taku Miyoshi, Naoki Shiraishi, Daisuke Kadowaki, Y Sakai, Masashi Mukoyama, Kenichiro Kitamura
  • Journal Title: Nephron Volume: 129 Issue: 3 Pages: 223-232
  • DOI: 10.1159/000375308
  • Peer Reviewed / Open Access / Acknowledgement Compliant