elucidation of physiological roles of prostasin and its signaling pathway

• Project/Area Number: 21591056
• 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: SHIRAISHI Naoki 熊本大学, 大学院・生命科学研究部, 助教 (40423660)
• 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: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); 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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: シグナル伝達 / 生体分子 / 生理活性

Research Abstract

We demonstrated that addition of recombinant prostasin to human adrenocortical cells increased secretion of aldosterone to the media in a dose dependent manner. We also showed that camostat mesilate, a potent serine-protease inhibitor, suppressed the progression of renal injury in aldosterone-induced renal injury model rats and in 5/6 nephrectomized renal failure model rats. Since camostat has been already clinically used as a medicine for pancreatitis and esophagitis in Japan, early clinical application of camostat for renal failure can be expected.

Research Products

• [Journal Article] Case of anti-glomerular basement membrane antibody-induced glomerulonephritis with cytomegalovirus-induced thrombotic microangiopathy (2012)
  • Author(s): Shiraishi-N, Kitamura-K, Hayata-M, Ogata-T, Adachi-M, Kajiwara-K, Ikeda-H, Miyoshi-T, Tomita-K
  • Journal Title: Internal medical Journal Volume: 42(3)
  • Peer Reviewed
• [Journal Article] Case of anti-glomerular basement membrane abntibody-induced glomerul onephritis with cytomegalovirus-induced thrombotic microangiopathy (2012)
  • Author(s): Shiraishi-N, et al
  • Journal Title: Intern Med J Volume: 42(3) Issue: 3
  • DOI: 10.1111/j.1445-5994.2011.02703.x
  • Peer Reviewed
• [Journal Article] A study of maintenance therapy after intravenous maxacalcitol for secondary hyperparathyroidism (2011)
  • Author(s): Adachi-M, Miyoshi-T, Shiraishi-N, Shimada-H, Sakaguchi-S, Tomita-K, Kitamura-K
  • Journal Title: Clin Nephrol Volume: 76(4) Pages: 266-72
  • 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] 【腎不全の最近の動向と阻止対策】腎硬化症 (2011)
  • Author(s): 白石直樹、冨田公夫
  • Journal Title: カレントテラピー Volume: 29(8) Pages: 677-686
• [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 Pages: 793843-793843
  • Peer Reviewed
• [Journal Article] Regulation of Adrenal aldosterone production by serine protease Prostasin (2010)
  • Author(s): Ko-T, et al.
  • Journal Title: Journal of Biomedicine and Biotechnology Volume: 2010 Pages: 1-9
  • Peer Reviewed
• [Journal Article] 腹部エコー検査 (2010)
  • Author(s): 白石直樹, 他
  • Journal Title: 腎と透析 Volume: 68巻5号 Pages: 792-795
• [Journal Article] Regulation of Adrenal aldosterone production by serine protease Prostasin (2010)
  • Author(s): Ko-T, et al.
  • Journal Title: Journal of Biomedicine and Biotechnology 2010 Pages: 1-9
  • 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 Volume: 27(8) Pages: 1679-89
  • Peer Reviewed
• [Journal Article] Aberrant ENaC activation in Dahl salt-sensitive rats (2009)
  • Author(s): Kakizoe-y, et al.
  • Journal Title: Journal of hypertension 27(8) Pages: 1679-89
  • 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): Uchimura-K, et al
  • Organizer: American Society of Nephrology Kidney Week 2011
  • Place of Presentation: Pennsylvania Convention Center (Philadelphia, U.S.A)
  • Year and Date: 2011-11-10
• [Presentation] A synthetic serine protease inhibitor camostat mesilate inhibited the proteolyic activation of gENaC in the kidney of the aldosterone-infused rats (2011)
  • Author(s): Morinaga-J, et al
  • Organizer: American Society of Nephrology Kidney Week 2011
  • Place of Presentation: Pennsylvania Convention Center (Philadelphia, U.S.A)
  • Year and Date: 2011-11-10
• [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, 北村健一郎, 内村幸平, 早田学, 森永潤, 尾上友朗, 水本輝彦, 安達政隆, 實吉拓, 白石直樹, 酒井芳紀, 冨田公夫
  • Organizer: 第54回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-06-16
• [Presentation] 腎硬化症、虚血性腎症の発症率と危険因子の同定に関する研究 (2011)
  • Author(s): 白石直樹, 冨田公夫
  • Organizer: 第54回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-06-16
• [Presentation] アルドステロンによる上皮型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, 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
  • Year and Date: 2011-06-16
• [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, 北村健一郎, 尾上友朗, 水本輝彦, 内村幸平, 早田学, 柿添豊, 安達政隆, 實吉拓, 白石直樹, 酒井芳紀, 冨田公夫
  • Organizer: 第54回日本腎臓学会学術総会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2011-06-15
• [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): Uchimura-K, Kakizoe-Y, Onoue-T, Hayata-M, Morinaga-J, Mizumoto-T, Adachi-M, Miyoshi-T, Shiraishi-N, Sakai-Y, Tomita-K, Kitamura-K
  • Organizer: American Society of Nephrology Kidney Week 2011
  • Place of Presentation: Pennsylvania Convention Center, Philadelphia, PA
• [Presentation] A synthetic serine protease inhibitor camostat mesilate attenuates renal interstitial fibrosis in rats (2011)
  • Author(s): Morinaga-J, Kakizoe-Y, Miyoshi-T, Onoue-T, Mizumoto-T, Hayata-M, Uchimura-K, Shiraishi-N, Adachi-M, Sakai-Y, Tomita-K, Kitamura-K
  • Organizer: American Society of Nephrology Kidney Week 2011
  • Place of Presentation: Pennsylvania Convention Center, Philadelphia, PA
• [Presentation] ラット腎虚血再灌流障害におけるセリンプロテアーゼの役割 (2010)
  • Author(s): 早田学, 北村健一郎, 柿添豊, 内村幸平, 森永潤, 安達政隆, 白石直樹, 實吉拓, 冨田公夫, 酒井芳紀
  • 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: 2010-06-17
• [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, 早田学, 森永潤, 安達政隆, 白石直樹, 實吉拓, 酒井芳紀, 冨田公夫
  • 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: 2010-06-17
• [Presentation] Regulation of Adrenal aldosterone production by serine protease Prostasin (2010)
  • Author(s): Kitamura-K, et al.
  • Organizer: 14^<th> International Congress of Endocrinology
  • Place of Presentation: Kyoto, Japan(国立京都国際会館)
  • Year and Date: 2010-03-30