Mechanism of prostasin-induced aldosterone production

• Project/Area Number: 20390238
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kumamoto University
• Principal Investigator: TOMITA Kimio Kumamoto University, 大学院・生命科学研究部, 教授 (40114772)
• Co-Investigator(Kenkyū-buntansha): KITAMURA Kenichiro 熊本大学, 医学部附属病院, 講師 (10304990)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2010: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2009: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000); Fiscal Year 2008: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
• Keywords: 高血圧 / 腎 / ナトリウム / アルドステロン / プロスタシン / セリンプロテアーゼ / プロセッシングエンザイム

Research Abstract

The control of blood pressure (BP) and extracellular fluid volume primarily depends on renal regulation of sodium reabsorption and excretion. The epithelial sodium channel (ENaC) plays an important role in the regulation of blood pressure by modulating Na reabsorption in the kidney. We previously revealed that prostasin increased Na transport through ENaC in the co-expression system using Xenopus oocytes, and that aldosterone increased the abundance of prostasin in human and rat urine and in the cultured medium of a mouse cortical collecting duct cell line.
We examine if prostasin increases the aldosterone synthesis in a human adrenocortical cell line (H295R cells). Luciferase assay using CYP11B2 promoter is used to see if the prostasin increases the transcriptional activity of CYP11B2. In addition, ENaC activity is investigated in Dahl hypertensive rats which are the model animal of salt-sensitive hypertension.

Research Products

• [Journal Article] Aldosterone requires vasopressin vla receptors on intercalated cells to mediate Acid-base homeostasis. (2011)
  • Author(s): Izumi, Y., Hori, K., Nakayama, Y., Kimura, M., Hasuike, Y., Nanami, M., Kohda, Y., Otaki, Y., Kuragano, T., Obinata, M., Kawahara, K., Tanoue, A., Tomita, K., Nakanishi, T., Nonoguchi, H.
  • Journal Title: J Am Soc Nephrol. 22(4) Pages: 673-680
  • 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): Makoto Anraku, M., Takeuchi, K.,Watanabe, H., Kadowaki, D., Kitamura, K., Tomita, K., Kuniyasu, A., Suenaga, A., Maruyama, T., Otagiril, M.
  • Journal Title: J.Pharm.Sci. in press
  • Peer Reviewed
• [Journal Article] A case of anti-glomerular basement membrane antibody-induced glomerulonephritis with cytomegalovirus-induced thrombotic microangiopathy. (2011)
  • Author(s): Shiraishi, N., Kitamura, K., Hayata, M., Ogata, T., Adachi, M., Kajiwara, K., Ikeda, H., Miyoshi, T., Tomita, K.
  • Journal Title: Intern.Med.J. in press
  • Peer Reviewed
• [Journal Article] Aldosterone requires vasopressin vla receptors on intercalated cells to mediate Acid-base homeostasis. (2011)
  • Author(s): Izumi, Y., 他
  • Journal Title: J Am Soc Nephrol. Volume: 22 Pages: 673-680
  • Peer Reviewed
• [Journal Article] Regulation of renal sodium handling through the interaction between serine proteases and serine protease inhibitors. (2010)
  • Author(s): Kitamura K, Tomita K
  • Journal Title: Clin Exp Nephrol. 14 Pages: 405-10
  • NAID: 10027706988
  • Peer Reviewed
• [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: 793843-793843
  • Peer Reviewed
• [Journal Article] Human sodium-phosphate transporter hNPT4(SLC17A3) as a common renal secretory pathway for drugs and urate. (2010)
  • Author(s): P Jutabha, N Anzai, K Kitamura, A Taniguchi, S Kaneko, H Yamada, H Shimada, T Kimura, T Katada, T Fukutomi, K Tomita, W Urano, H Yamanaka, G Seki, T Fujita, K Yan, A Yamada, S Uchida, M F.Wempe, H Endou, H Sakurai.
  • Journal Title: JBC 285 Pages: 35123-35132
  • Peer Reviewed
• [Journal Article] Regulation of renal sodium handling through the interaction between serine proteases and serine protease inhibitors (2010)
  • Author(s): Kitamura, K., 他
  • Journal Title: Clin.Exp.Nephrol. Volume: 14 Pages: 405-410
  • NAID: 10027706988
  • Peer Reviewed
• [Journal Article] The Epithelium-Molecular Landscaping for an Interactive Barrier (2010)
  • Author(s): Chai, K., 他
  • Journal Title: J.Biomed.Biotech. Volume: 2010 Pages: 870506-870506
  • Peer Reviewed
• [Journal Article] Regulation of adrenal aldosterone production by serine protease prostasin. (2010)
  • Author(s): Ko T, 他
  • Journal Title: J Biomed Biotechnol. 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., 他
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 35123-35132
  • Peer Reviewed
• [Journal Article] A case with acute renal failure and subsequent nephrotic syndrome. (2009)
  • Author(s): Nonoguchi H, Kohda Y, Fukutomi R, Nakayama Y, Naruse M, Kitamura K, Inoue T, Nakanishi T, Tomita K.
  • Journal Title: Ren Fail. 31(2) Pages: 162-166
  • Peer Reviewed
• [Journal Article] Low pH stimulates vasopressin V2 receptor promoter activity and enhances downregulation induced by V1a receptor stimulation. (2009)
  • Author(s): Memetimin H, Izumi Y, Nakayama Y, Kohda Y, Inoue H, Nonoguchi H, Tomita K.
  • Journal Title: Am J Physiol Renal Physiol. 297(3)
  • 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(8) Pages: 1679-89
  • Peer Reviewed
• [Journal Article] Urinary prostasin in humans : relationships among prostasin, aldosterone and epithelial sodium channel activity. (2009)
  • Author(s): Koda A, Wakida N, Toriyama K, Yamamoto K, Iijima H, Tomita K, Kitamura K.
  • Journal Title: Hypertens Res. 32(4) Pages: 276-281
  • NAID: 10024830568
  • Peer Reviewed
• [Journal Article] Revised Equations for Estimated GFR From Serum Creatinine in Japan. on behalf of the collaborators developing the Japanese equation for estimated GFR. (2009)
  • Author(s): Matsuo S, Imai E, Horio M, Yasuda Y, Tomita K, Nitta K, Yamagata K, Tomino Y, Yokoyama H, Hishida A
  • Journal Title: Am J Kidney Dis. Epub ahead of print
  • Peer Reviewed
• [Journal Article] Acute and chronic metabolic acidosis interferes with aquaporin-2 translocation in the rat kidney collecting ducts. (2009)
  • Author(s): Mouri T, Inoue T, Nonoguchi H, Nakayama Y, Miyazaki H, Matsuzaki T, Saito H, Nakanishi T, Kohda Y, Tomita K.
  • Journal Title: Hypertens Res. 32(5) Pages: 358-363
  • NAID: 10026122512
  • Peer Reviewed
• [Journal Article] Different Mechanisms for the Progression of CKD with ACE Gene Polymorphisms. (2009)
  • Author(s): Nakayama Y, Nonoguchi H, Kohda Y, Inoue H, Memetimin H, Izumi Y, Tomita K.
  • Journal Title: Nephron Clin Pract. 111(4)
  • 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, Kakizoe Y, Miyoshi T, Wakida N, Ko T, Shiraishi N, Adachi M, Tomita K, Kitamura K.
  • Journal Title: J Hypertens. 27(1) Pages: 181-189
  • Peer Reviewed
• [Journal Article] Vasopressin and hyperosmolality regulate NKCC1 expression in rat OMCD. (2009)
  • Author(s): Wakamatsu S, Nonoguchi H, Ikebe M, Machida K, Izumi Y, Memetimin H, Nakayama Y, Nakanishi T, Kohda Y, Tomita K.
  • Journal Title: Hypertens Res. 32 Pages: 481-487
  • NAID: 10024831162
  • Peer Reviewed
• [Journal Article] High serum alanine aminotransferase levels for the first three successive years can predict very high incidence of hepatocellular carcinoma in patients with Child Stage A HCV-associated liver cirrhosis. (2009)
  • Author(s): Miyakawa K, Tarao K, Ohshige K, Morinaga S, Ohkawa S, Okamoto N, Shibuya A, Adachi S, Miura Y, Fujiyama S, Miyase S, Tomita K.
  • Journal Title: Scand J Gastroenterol. 44(11) Pages: 1340-1348
  • Peer Reviewed
• [Journal Article] Urinary prostasin in humans : relationships among prostasin, aldosterone and epithelial sodium channel activity (2009)
  • Author(s): Koda A, 他
  • Journal Title: Hepertens Res. 32(4) Pages: 276-81
  • 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, 他
  • Journal Title: J Hypertens. 27(1) Pages: 181-9
  • Peer Reviewed
• [Journal Article] Aberrant ENaC activation in Dahl salt-sensitive rats (2009)
  • Author(s): Kakizoe Y, 他
  • Journal Title: J Hypertens. 27(8) Pages: 1679-89
  • Peer Reviewed
• [Journal Article] Effect of intravenous iron administration frequency on AOPP and inflammatory biomarkers in chronic hemodialysis patients : a pilot study. (2008)
  • Author(s): Anraku M, Kitamura K, Shintomo R, Takeuchi K, Ikeda H, Nagano J, Ko T, Mera K, Tomita K, Otagiri M.
  • Journal Title: Clin Biochem. 41(14-15) Pages: 1168-1174
  • NAID: 120005952925
  • Peer Reviewed
• [Journal Article] Regulation of V2R transcription by hypertonicity and V1aR-V2R signal interaction. (2008)
  • Author(s): Izumi Y, Nakayama Y, Memetimin H, Inoue T, Kohda Y, Nonoguchi H, Tomita K.
  • Journal Title: Am J Physiol Renal Physiol. 295(4)
  • Peer Reviewed
• [Journal Article] Long-term observation of renal function on combination therapy with prostaglandin and angiotensin-converting enzyme inhibitor for chronic kidney disease. (2008)
  • Author(s): Nakayama Y, Inoue T, Kohda Y, Inoue H, Izumi Y, Tomita K, Nonoguchi H.
  • Journal Title: Clin Nephrol. 69(6) Pages: 402-407
  • Peer Reviewed
• [Journal Article] Vasopressin regulates the renin-angiotensin-aldosterone system via V1a receptors in macula densa cells. (2008)
  • Author(s): Aoyagi T, Izumi Y, Hiroyama M, Matsuzaki T, Yasuoka Y, Sanbe A, Miyazaki H, Fujiwara Y, Nakayama Y, Kohda Y, Yamauchi J, Inoue T, Kawahara K, Saito H, Tomita K, Nonoguchi H, Tanoue A.
  • Journal Title: Am J Physiol Renal Physiol. 295(1)
  • Peer Reviewed
• [Journal Article] Functional and immunochemical characterization of a novel organic anion transporter Oat8 (Slc22a9) in rat renal collecting duct. (2008)
  • Author(s): Yokoyama H, Anzai N, Ljubojevic M, Ohtsu N, Sakata T, Miyazaki H, Nonoguchi H, Islam R, Onozato M, Tojo A, Tomita K, Kanai Y, Igarashi T, Sabolic I, Endou H.
  • Journal Title: Cell Physiol Biochem. 21(4) Pages: 269-278
  • Peer Reviewed
• [Journal Article] Altered pharmacokinetics of cationic drugs caused by down-regulation of renal rat organic cation transporter 2 (Slc22a2) and rat multidrug and toxin extrusion 1 (Slc47a1) in ischemia/reperfusion-induced acute kidney injury. (2008)
  • Author(s): Matsuzaki T, Morisaki T, Sugimoto W, Yokoo K, Sato D, Nonoguchi H, Tomita K, Terada T, Inui K, Hamada A, Saito H.
  • Journal Title: Drug Metab Dispos. 36(4) Pages: 649-654
  • Peer Reviewed
• [Journal Article] Long-term plasma levels and dose modulation of alacepril in patients with chronic renal failure. (2008)
  • Author(s): Nonoguchi H, Kiyama S, Kitamura K, Naruse M, Tomita M, Tazoe N, Tajiri M, Nakayama Y, Kohda Y, Inoue T, Tomita K.
  • Journal Title: Hypertens Res. 31(1) Pages: 29-36
  • NAID: 10021260933
  • Peer Reviewed
• [Journal Article] Regulation of V2R transcription by hypertonicity and V1aR-Y2R signal interaction. (2008)
  • Author(s): Izumi Y, 他
  • Journal Title: Am J Physiol Renal Physiol. 295
  • Peer Reviewed
• [Journal Article] Vasopress in regulates the renin-angiotensin-aldosterone system via vla receptors in macula densa cells. (2008)
  • Author(s): Aoyagi T, 他
  • Journal Title: Am J Physiol Renal Physiol. 295
  • Peer Reviewed
• [Journal Article] Functional and immunochemical characterization of a novel organic anion transporter Oat8 (Slc22a9)in rat renal collecting duct. (2008)
  • Author(s): Yokoyama H, 他
  • Journal Title: Cell Physiol Biochem. 21 Pages: 269-78
  • Peer Reviewed
• [Journal Article] A study of maintenance therapy after intravenous maxacalcitol for secondary hyperparathyroidism.
  • Author(s): Adachi, M., Miyoshi, T., Shiraishi, N., Shimada, H., Sakaguchi, S., Tomita, K., Kitamura, K.
  • Journal Title: Clin.Nephrol. in press
  • Peer Reviewed
• [Journal Article] The MAXIMA trial.
  • Author(s): H.Nonoguchi, Y.Izumi, Y.Nakayama, Y.Kohda, K.Tomita.
  • Journal Title: Lancet. 371 Pages: 299-300
  • Peer Reviewed