Involvement of serine proteases in aldosterone-induced renal injury.

2010 Fiscal Year Final Research Report

• Project/Area Number: 20590977
• 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: ADACHI Masataka Kumamoto University, 医学部附属病院, 助教 (90398206)
• Project Period (FY): 2008 – 2010
• Keywords: 循環器・高血圧 / 生体分子 / 薬学 / 臨床

Research Abstract

Aldosterone has been recently reported to have harmful effects on many organs independent of its hemodynamic effect. However the mechanisms of these effects have not been well understood.
We once reported that the administration of a synthetic serine protease inhibitor camostat mesilate lowered the elevated blood pressure and attenuated kidney injury in Dah1 salt-sensitive rats. So it would be highly probable that serine proteases are involved in the pathogenesis of salt-sensitive hypertension and organ damages. In this study, in order to elucidate the role of serine proteases in the kidney injury induced by aldosterone and salt, we administrated camostat to aldosterone/salt-treated uninephrectomized rats. As camostat ameliorated glomeruloscrelosis and tublointerstitial fibrosis in these rats, we searched and detected one serine protease which was induced by aldosterone/salt. Our results suggest that a serine protease is highly related to kidney injury induced by aldosterone/salt, and serine protease inhibitor could be a new strategy for the treatment of kidney injury associated with aldosterone in human.

Research Products

• [Journal Article] Regulation of adrenal aldosterone production by serine protease prostasin. (2010)
  • Author(s): Ko, T., Kakizoe, Y., Wakida, N., Hayata, M., Uchimura, K., Shiraishi, N., Miyoshi, T., Adachi, M., Aritomi, S., Konda, T., Tomita, K., Kitamura, K.
  • Journal Title: J Biomed Biotechnol. 2010 Pages: 793843
  • Peer Reviewed
• [Journal Article] Aberrant ENaC activation in Dahl salt-sensitive rats. (2009)
  • Author(s): Kakizoe, Y., Kitamura, K., Ko, T., Wakida, N., Maekawa, A., Miyoshi, T., Shiraishi, N., Adachi, M., Zhang, Z., Masilamani, S., Tomita, K.
  • 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. (2008)
  • Author(s): Maekawa, A., Kakizoe, Y., Miyoshi, T., Wakida, N., Ko, T., Shiraishi, N., Adachi, M., Tomita, K., Kitamura, K.
  • Journal Title: J hypertens. 26 Pages: 1-10
  • Peer Reviewed
• [Presentation] アルドステロンによる腎障害に対するメシル酸カモスタットの効果 (2010)
  • Author(s): 柿添豊、北村健一郎、内村幸平、森永潤、安達政隆, 他
  • Organizer: 第53回日本腎臓学会学術総会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2010-06-16
• [Presentation] プロスタシンによるアルドステロン産生誘導 (2008)
  • Author(s): 健博、北村健一郎、脇田直樹、柿添豊、安達政隆, 他
  • Organizer: 第51回日本腎臓学会学術総会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2008-06-01
• [Presentation] 柿添豊、前川愛、北村健一郎、脇田直樹、?健博、安達政隆, 他 (2008)
  • Author(s): 食塩感受性高血圧に対するセリンプロテアーゼ阻害薬の降圧効果
  • Organizer: 第51回日本腎臓学会学術総会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2008-05-30
• [Remarks] ホームページ等
  • URL: http://www2.kuh.kumamoto-u.ac.jp/nephrology/