A comprehensive analysis of serine proteases involved in the renal injury induced by aldosterone and salt loading

• Project/Area Number: 21591035
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kumamoto University
• Principal Investigator: KITAMURA Kenichiro 熊本大学, 大学院・生命科学研究部, 准教授 (10304990)
• Co-Investigator(Kenkyū-buntansha): TOMITA Kimio 熊本大学, 大学院・生命科学研究部, 教授 (40114772)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 腎臓学 / アルドステロン / セリンプロテアーゼ / 腎障害 / 高血圧 / ナトリウムチャネル / プロスタシン

Research Abstract

Aldosterone has been demonstrated to induce severe organ damage to animals when administered with high salt diet. We demonstrated that a serine protease inhibitor significantly reduced the progression of renal injury induced by aldosterone and high salt diet, suggesting that serine proteases are involved in the development of renal injury. We isolated plasmin as a candidate serine protease involved in the aldosterone induced renal injury.

Research Products

• [Journal Article] Clinical and functional characterization of URAT1 variants (2011)
  • Author(s): Tasic, V., Hynes, A. M., Kitamura, K., et al
  • Journal Title: PLoS One Volume: 6
  • Peer Reviewed
• [Journal Article] A study of maintenance therapy after intravenous maxacalcitol for secondary hyperparathyroidism (2011)
  • Author(s): Adachi, M., Tomita, K., Kitamura, K., et al
  • Journal Title: Clin. Nephrol. Volume: 76 Pages: 266-272
  • Peer Reviewed
• [Journal Article] Cys34 on antioxidative propertie of HSA quantitative analysis of cysteine-34 on the anitioxidative properties of human serum albumin in hemodialysis patients (2011)
  • Author(s): Anraku, M., Kitamura, K., Tomita, K., et al
  • Journal Title: J. Pharm. Sci. Volume: 100 Pages: 3968-3976
  • Peer Reviewed
• [Journal Article] Cys34 on antioxidative propertie of HSA quantitative analysis of cysteine-34 on the anitioxidative properties of human serum albumin in hemodialysis patients (2011)
  • Author(s): Anraku, M., et al
  • Journal Title: J.Pharm.Sci. Volume: 100 Issue: 9 Pages: 3968-3976
  • DOI: 10.1002/jps.22571
  • Peer Reviewed
• [Journal Article] A study of maintenance therapy after intravenous maxacalcitol for secondary hyperparathyroidism (2011)
  • Author(s): Adachi M., et al
  • Journal Title: Clin.Nephrol. Volume: 76 Issue: 10 Pages: 266-272
  • DOI: 10.5414/cn106595
  • Peer Reviewed
• [Journal Article] Clinical and functional characterization of URAT1 variants (2011)
  • Author(s): Tasic V, Hynes AM, Kitamura K, Cheong HI, Lozanovski VJ, Gucev Z, Jutabha P, Anzai N, Sayer JA
  • Journal Title: PLoS One Volume: 6 Issue: 12 Pages: e28641-e28641
  • DOI: 10.1371/journal.pone.0028641
  • Peer Reviewed
• [Journal Article] Regulation of renal sodium handling through the interaction between serine proteases and serine protease inhibitors (2010)
  • Author(s): Kitamura, K. and Tomita, K.
  • Journal Title: Clin. Exp. Nephrol. Volume: 14 Pages: 405-410
  • NAID: 10027706988
  • Peer Reviewed
• [Journal Article] Regulation of adrenal aldosterone production by serine protease prostasin (2010)
  • Author(s): Ko, T., Tomita, K., Kitamura, K., et al
  • Journal Title: J. Biomed. Biotech. Volume: 2010 Pages: 793843-793843
  • Peer Reviewed
• [Journal Article] Human sodium-phosphate transporter 4(hNPT4/SLC17A3) as a common renal secretory pathway for drugs and urate (2010)
  • Author(s): Jutabha, P., Kitamura, K., Tomita, K., et al
  • Journal Title: J. Biol. Chem. Volume: 285 Pages: 35123-35132
  • Peer Reviewed
• [Journal Article] Human sodium-phosphate transporter 4 (hNPT4/SLC17A3) as a common renal secretory pathway for drugs and urate. (2010)
  • Author(s): Jutabha, P., et al
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 35123-35132
  • Peer Reviewed
• [Journal Article] Regulation of adrenal aldosterone production by serine protease prostasin (2010)
  • Author(s): Ko, T., et al
  • Journal Title: J.Biomed.Biotech. Volume: 2010 Pages: 793843-793843
  • Peer Reviewed
• [Journal Article] Aberrant ENaC activation in Dahl salt-sensitive rats (2009)
  • Author(s): Kakizoe, Y., Kitamura, K., Tomita, K., et al
  • Journal Title: J. Hypertens. Volume: 27 Pages: 1679-1689
  • Peer Reviewed
• [Journal Article] Urinary prostasin in humans : relationships among prostasin, aldosterone and epithelial sodium channel activity (2009)
  • Author(s): Koda, A., Tomita, K., Kitamura, K., et al
  • Journal Title: Hypertens. Res. Volume: 32 Pages: 267-281
  • NAID: 10024830568
  • Peer Reviewed
• [Journal Article] Camostat mesilate inhibits prostasin activity, and reduces blood pressure and renal injury in salt-sensitive hypertension (2009)
  • Author(s): Maekawa, A., Tomita, K., Kitamura, K., et al
  • Journal Title: J. Hypertens. Volume: 27 Pages: 181-189
  • Peer Reviewed
• [Journal Article] Aberrant ENaC activation in Dahl salt-sensitive rats (2009)
  • Author(s): Kakizoe Y, et al
  • Journal Title: J.Hypertens 27 Pages: 1679-1689
  • Peer Reviewed
• [Journal Article] Camostat mesilate inhibits prostasin activity, and reduces blood pressure and renal injury in salt-sensitive hypertension (2009)
  • Author(s): Maekawa A, et al
  • Journal Title: J.Hypertens 27 Pages: 181-189
  • Peer Reviewed
• [Journal Article] Urinary prostasin in humans : relationships among prostasin, aldosterone and epithelial sodium channel activity (2009)
  • Author(s): Koda A, et al
  • Journal Title: Hypertens.Res. 32 Pages: 267-281
  • Peer Reviewed
• [Presentation] A Synthetic Serine Protease Inhibitor Camostat Mesilate Inhibited the Proteolytic Activation of gENaC in the Kidney of the Aldosterone-Infused Rats (2011)
  • Author(s): K. Uchimura
  • Organizer: Kidney Week 2011
  • Place of Presentation: フィラデルフィア、米国
  • Year and Date: 2011-11-11
• [Presentation] A Synthetic Serine Protease Inhibitor Camostat Mesilate Attenuates Renal Interstitial Fibrosis in Rats (2011)
  • Author(s): J. Morinaga
  • Organizer: Kidney Week 2011
  • Place of Presentation: フィラデルフィア、米国
  • Year and Date: 2011-11-11
• [Presentation] 片側尿管結紮モデル(UUO)ラットにおけるメシル酸カモスタットの効果 (2011)
  • Author(s): 森永潤, 他
  • Organizer: 第54回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2011-06-15
• [Presentation] アルドステロンによる上波型Naチャネル活性化におけるセリンプロテアーゼ阻害薬の効果 (2011)
  • Author(s): 柿添豊
  • Organizer: 第54回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川)
  • Year and Date: 2011-05-15
• [Presentation] 片側尿管結紮モデルラットにおけるメシル酸カモスタットの効果 (2011)
  • Author(s): 森永潤
  • Organizer: 第54回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川)
  • Year and Date: 2011-05-15
• [Presentation] Serine Protease Inhibitor Attenuates Hypertension and Kidney Injury in Dahl Salt-Sensitive Rats (2009)
  • Author(s): Kakizoe Y, et al
  • Organizer: IUPS2009
  • Place of Presentation: 京都国際会館
  • Year and Date: 2009-07-31
• [Book] 薬剤性AKI (2011)
  • Author(s): 早田学、北村健一郎
• [Book] AKI保存的治療における体液・電解質管理について (2010)
  • Author(s): 早田学、北村健一郎
• [Book] Prostasin (2010)
  • Author(s): 早田学、北村健一郎
• [Book] アルドステロンの標的分子 (2010)
  • Author(s): 柿添豊、北村健一郎
• [Remarks]
  • URL: http://www.kumadai-nephrology.com/