The mechanisms of regulation of nuclocytoplasmic transport of mineralocorticoid receptor by vasopressin V1a receptor.

• Project/Area Number: 24591244
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Kitasato University
• Principal Investigator: NONOGUCHI Hiroshi 北里大学, 北里大学メディカルセンター, 副院長 (30218341)
• Co-Investigator(Kenkyū-buntansha): NAKANISHI Takeshi 兵庫医科大学, 医学部, 教授 (70217769)
• Co-Investigator(Renkei-kenkyūsha): KAWAHARA Katsumasa 北里大学, 医学部, 教授 (70134525) ; NAKAYAMA Yushi 熊本大学, 医学部, 准教授 (00363531) ; YASUOKA Yukiko 北里大学, 医学部, 講師 (50348504) ; IZUMI Yuichiro 熊本大学, 医学部, 研究員 (20736243)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: アルドステロン / バゾプレッシン / ミネラルコルチコイド受容体 / バゾプレッシンV1a受容体 / 核内受容体 / 間在細胞 / small G protein / 酸塩基平衡 / エリスロポエチン / 低酸素 / 貧血 / Hypoxia inducible factor / in situ hybridization / NKCC2 / 心房性ナトリウム利尿ペプチド / 集合尿細管 / ミネラルコルチコイドレセプター / 酸排泄 / 腎集合尿細管間在細胞

Outline of Final Research Achievements

We showed that aldosterone stimulated nucleocytoplasmic transport of mineralocorticoid receptor (MR) in rat intercalated cells using immunohistochemistry and Wester blot. Aldoterone was found to stimulate RCC-1 acticvity, whereas vasopressin decreases the activation of Ran Gap1. The presence of vasopressin V1a receptor was required for the stimulation of nucleocytoplasmic transpoort of MR.
Aldosterone and vasopressin stimulate PKC pathway. However, aldosterone stimulates atyoical or novel PKC pathways whereas vasopressin stimulate conventional PKC pathway. Although EGF receotor has been thought to be a membrane-bound receptor of aldosterone, further investigations are required to draw the conclusion.

Research Products

• [Journal Article] pH-sensitive expression of calcium-sensing receptor (CaSR) in type-B intercalated cells of the cortical collecting ducts (CCD) in mouse kidney. (2015)
  • Author(s): Yasuoka Y, Nonoguchi H, Kawahara K, et al.
  • Journal Title: Clin Exp Nephrol Volume: 18
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Reevaluation of erythropoietin production by the nephron (2014)
  • Author(s): Nagai T, Yasuoka Y, Kawahara K, Nonoguchi H, et al.
  • Journal Title: Biochem Biophys Res Commun. Volume: 449 Issue: 3 Pages: 222-228
  • DOI: 10.1016/j.bbrc.2014.09.089
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Expression of three isoforms of Na-K-2Cl cotransporter (NKCC2) in the kidney and regulation by dehydration.. (2014)
  • Author(s): Itoh K, Izumi Y, Kawahara K, Nonoguchi H, et al.
  • Journal Title: Biochem Biophys Res Commun. Volume: 453 Issue: 2 Pages: 356-361
  • DOI: 10.1016/j.bbrc.2014.05.014
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Combined angiotensin inhibition in diabetic nephropathy. (2014)
  • Author(s): Izumi Y, Kawahara K, Nonoguchi H.
  • Journal Title: N Engl J Med Volume: 370 Issue: 8 Pages: 777-778
  • DOI: 10.1056/nejmc1315504
  • Peer Reviewed
• [Journal Article] Mistargeting of proxisomal EHHADH and inherited renal Fanconi’s syndrome. (2014)
  • Author(s): Klootwijk ED, Reichold M, Helip-Wooley A, Tolaymat A, Izumu Y, Nonoguchi H, Kleta R, et al.
  • Journal Title: N Engl J Med Volume: 370 Issue: 2 Pages: 129-138
  • DOI: 10.1056/nejmoa1307581
  • Peer Reviewed
• [Journal Article] Effects of Atrial Natriuretic Peptide on Bicarbonate Transport in Long- and Short-Looped Medullary Thick Ascending Limbs of Rats. (2013)
  • Author(s): Hiroshi Nonoguchi, Yuichiro Izumi, Yushi Nakayama, Takanobu Matsuzaki , Yukiko Yasuoka, Takeaki Inoue, Hideaki Inoue, Tomohiko Mouri, Katsumasa Kawahara, Hideyuki Saito, Kimio Tomita.
  • Journal Title: PLOS one. Volume: 8 Issue: 12 Pages: e83146-e83146
  • DOI: 10.1371/journal.pone.0083146
  • Peer Reviewed
• [Journal Article] The intercalated cells of the mouse kidney OMCDis are the target of the vasopressin V1a receptor axis for urinary acidification (2013)
  • Author(s): Yasuoka Y, Kobayashi M, Sato Y, Zhou M, Abe H, Okamoto H, Nonoguchi H, Tanoue A, Kawahara K
  • Journal Title: Clin Exp Nephrol Volume: 17 Issue: 6 Pages: 783-792
  • DOI: 10.1007/s10157-013-0783-y
  • Peer Reviewed
• [Journal Article] Decreased expression of aquaporin 2 in the collecting duct of mice lacking the vasopressin V1a receptor (2013)
  • Author(s): Yasuoka Y, Kobayashi M, Sato Y, Nonoguchi H, Tanoue A, Okamoto H, Kawahara K
  • Journal Title: Clin Exp Nephrol Volume: 17 Issue: 2 Pages: 183-190
  • DOI: 10.1007/s10157-012-0686-3
  • NAID: 10031169465
  • Peer Reviewed
• [Journal Article] Association of chronic kidney disease with adverse outcomes. (2013)
  • Author(s): Izumi Y, Ogawa M, Itoh H, Shimada H, Nonoguchi H.
  • Journal Title: Lancet Volume: 381 Issue: 9866 Pages: 531-531
  • DOI: 10.1016/s0140-6736(13)60271-8
  • Peer Reviewed
• [Journal Article] Vasopressin V1a and V1b receptors: from molecules to physiological systems (2012)
  • Author(s): T.A. Koshimizu, K. Nakamura, N. Egashira, M. Hiroyama, H. Nonoguchi, A. Tanoue
  • Journal Title: Physiological reviews Volume: 92 Issue: 4 Pages: 1813-1864
  • DOI: 10.1152/physrev.00035.2011
  • Peer Reviewed
• [Journal Article] Vasopressin V1a receptor is required for nucleocytoplasmic transport of mineralocorticoid receptor. (2012)
  • Author(s): Hori K, Nagai T, Izumi Y, Kimura M, Hasuike Y, Nakayama Y, Nanami M, Tokuyama M, Otaki Y, Kuragano T, Kohda Y, Obinata M, Kawahara K, Tanoue A, Tomita K, Nakanishi T, Nonoguchi H.
  • Journal Title: Am J Physiol. Volume: 303 Issue: 7 Pages: 1080-1088
  • DOI: 10.1152/ajprenal.00052.2012
  • Peer Reviewed
• [Journal Article] High levels of tumor necrosis factor-α downregulate antimicrobial iron transport protein, Nramp1, in chronic hemodialysis patients: a key factor for infection risk. (2012)
  • Author(s): Moriguchi R, Otaki Y, Hazeki S, Shimada T, Matsumoto A, Kakita N, Kaibe S, Kuragano T, Nonoguchi H, Masayoshi N, Hasuike Y, Nakanishi T.
  • Journal Title: Am J Nephrol. Volume: ３５ Issue: 4 Pages: 372-378
  • DOI: 10.1159/000337742
  • Peer Reviewed
• [Journal Article] The impact of ferritin fluctuations on stable hemoglobin levels in hemodialysis patients. (2012)
  • Author(s): Yahiro M, Kuragano T, Kida A, Kitamura R, Furuta M, Hasuike Y, Otaki Y, Nonoguchi H, Nakanishi T.
  • Journal Title: Clin Exp Nephrol. Volume: 16 Issue: 3 Pages: 448-455
  • DOI: 10.1007/s10157-011-0584-0
  • NAID: 10030808613
  • Peer Reviewed
• [Presentation] Erythropoietin production by the nephron. (2015)
  • Author(s): Nonoguchi H, Izumi Y, Yasuoka Y, Kawahara K.
  • Organizer: Kitasato-Yale Fluid Symposium
  • Place of Presentation: 北里大学薬学部（東京都港区白金）
  • Year and Date: 2015-03-02
• [Presentation] Erythropoietin production by the nephron. (2014)
  • Author(s): Izumi Y, Yasuoka Y, Nagai T, Kawahara K, Nonoguchi H, et al.
  • Organizer: Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Philadelphia (USA)
  • Year and Date: 2014-11-13 – 2014-11-16
• [Presentation] Hypercalcemia in mice with high CaP diet co-operatively stimulated (2014)
  • Author(s): Yasuoka Y, Nonoguchi H, Kawahara K, et al.
  • Organizer: Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Philadelphia (USA)
  • Year and Date: 2014-11-13 – 2014-11-16
• [Presentation] 腎尿細管におけるエリスロポエチン産生とアルドステロンによる制御機構 (2014)
  • Author(s): 泉裕一郎、安岡有紀子、河原克雅、野々口博史ら
  • Organizer: 日本腎臓学会総会
  • Place of Presentation: パシフィコ横浜 （神奈川県・横浜市）
  • Year and Date: 2014-07-04 – 2014-07-06
• [Presentation] Ca塩摂取時の腎結石予防と酸塩基調節：腎集合管Ca感受性受容体(CaSR)の役割 (2014)
  • Author(s): 安岡有紀子、河原克雅、野々口博史ら
  • Organizer: 日本腎臓学会総会
  • Place of Presentation: パシフィコ横浜 （神奈川県・横浜市）
  • Year and Date: 2014-07-04 – 2014-07-06
• [Presentation] Mechanisms of erythropoietin production by aldosterone in the intercalated cells. (2013)
  • Author(s): Izumi Y, Yasuoka Y, Nagai T, Hori K, Nakayama Y, Nanami M, Nakanishi T, Tanoue A, Tomita K, Kawahara K, Nonoguchi H.
  • Organizer: Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Georgia Convention Center (Atlanta, USA)
• [Presentation] Calcium Salts Affect Acid-Base Balance by Stimulating Differently Type A and B Intercalated Cells in Mouse Kidney Collecting Ducts (2013)
  • Author(s): Yasuoka Y, Sato Y, Nonoguchi H, Kawahara K
  • Organizer: Annual Meeting of the American Society of Nephrology
  • Place of Presentation: Georgia Convention Center (Atlanta, USA)
• [Presentation] 低酸素血症およびアルドステロンによる集合管の間在細胞におけるエリスロポエチンの産生機構 (2013)
  • Author(s): 永井孝憲、堀加穂理、泉祐一郎、中山裕史、倉賀野隆裕、富田公夫、河原克雅、田上昭人、野々口博史、中西健
  • Organizer: 第56回日本腎臓学会総会
  • Place of Presentation: 東京国際フォーラム（東京都千代田区）
• [Presentation] マウス腎集合管間在細胞（type B)におけるカルシウム感受性受容体(CaSR)の役割 (2013)
  • Author(s): 安岡有紀子、佐藤雄一、野々口博史、河原克雅
  • Organizer: 第56回日本腎臓学会総会
  • Place of Presentation: 東京国際フォーラム（東京都千代田区）
• [Presentation] Hypoxia and aldosterone stimulate erythropoietin production in intercalated cells of the collecting ducts
  • Author(s): Nagai T, Hori K, Izumi Y, Kimura M, Nakayama Y, Hasuike Y, Nanami M, Otaki Y, Kuragano T, Tomita K, Kawahara K, Tanoue T, Nakanishi T, Nonoguchi H.
  • Organizer: Annual Meeting of the American Society of Nephrology
  • Place of Presentation: San Diego
• [Presentation] バゾプレッシンV1aレセプターによるミネラルコルチコイドレセプター細胞質核内輸送制御機構
  • Author(s): 永井孝憲、堀加穂理、泉祐一郎、木村美穂、中山裕史、野々口博史ら
  • Organizer: 日本腎臓学会総会
  • Place of Presentation: 横浜
• [Presentation] Upregulation of mice carbonic anhydrase XII in the alpha-intercalated cell of outer medullary collecting duct during acidosis.
  • Author(s): Yasuoka Y, Sato Y, Nonoguchi H, Kawahara K.
  • Organizer: Annual Meeting of the American Society of Nephrology
  • Place of Presentation: San Diego
• [Book] Annual Review 腎臓2013 (2013)
  • Author(s): 野々口博史、中西健
  • Total Pages: 5
  • Publisher: 中外医学社