Novel hormones and receptors in renal and cardiovascular injuries.

• Project/Area Number: 21591016
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Tohoku Fukushi University
• Principal Investigator: TOTSUNE Kazuhito 東北福祉大学, 総合福祉学部, 教授 (10217515)
• Co-Investigator(Kenkyū-buntansha): TAKAHASHI Kazuhiro 東北大学, 大学院・医学系研究科, 教授 (80241628) ; IMAI Yutaka 東北大学, 大学院・薬学研究科, 教授 (40133946)
• 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: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 遺伝子 / 循環器 / 高血圧 / 腎障害 / 脳血管障害 / 循環器・高血圧 / 生理活性 / 発現・制御 / プロレニン受容体

Research Abstract

Pathophysiological roles of novel hormones and receptors were examined in association with organ injuries. Expressions of adrenomedullin II(AM2) and(pro) renin receptor((P) RR) in the kidney and/or heart were significantly changed in renal failure, cardiac failure and hypertensive animal models. Analyses of gene polymorphisms revealed that the polymorphisms of AM2 and(P) RR were significantly associated with occurrences of cardiac hypertrophy, cerebral lacuna infarction and chronic kidney diseases. These results indicate that these novel hormones and receptors actually play certain roles in the renal and cardiovascular injuries.

Research Products

• [Journal Article] Prognostic significance of home arterial stiffness index derived from self-measurement of blood pressure : the Ohasama Study (2012)
  • Author(s): Kikuya M, Totsune K, et al
  • Journal Title: Am J Hypertens Volume: 25 Issue: 1 Pages: 67-73
  • DOI: 10.1038/ajh.2011.167
  • Peer Reviewed
• [Journal Article] Influence of adrenomedullin 2/intermedin gene polymorphism on blood pressure, renal function and silent cerebrovascular lesions in Japanese : the Ohasama study (2011)
  • Author(s): Hirose T, Totsune K, Nakashige Y, Metoki H, Kikuya M, Ohkubo T, Hara A, Satoh M, Inoue R, Asayama K, Kondo T, Kamide K, Katsuya T, Ogihara T, Izumi Shin-Ichi, Rakugi H, Takahashi K and Imai Y.
  • Journal Title: Hypertens Res Volume: 34 Issue: 12 Pages: 1327-1332
  • DOI: 10.1038/hr.2011.131
  • NAID: 10030278155
  • Peer Reviewed
• [Journal Article] Association of(pro) renin receptor gene polymorphisms with lacunar infarction and left ventricular hypertrophy in Japanese women : the Ohasama study (2011)
  • Author(s): Hirose T, Hashimoto M, Totsune K, Metoki H, Hara A, Satoh M, Kikuya M, Ohkubo T, Asayama K, Kondo T, Kamide K, Katsuya T, Ogihara T, Izumi S, Rakugi H, Takahashi K, Imai Y.
  • Journal Title: Hypertens Res Volume: Vol.34 Pages: 530-535
  • NAID: 10031163212
  • Peer Reviewed
• [Journal Article] Adrenomedullin 2/intermedin in the hypothalamo-pituitary-adrenal axis (2011)
  • Author(s): Takahashi K, Morimoto R, Hirose T, Satoh F, Totsune K.
  • Journal Title: J Mol Neurosci Volume: Vol.43 Pages: 182-192
  • Peer Reviewed
• [Journal Article] Association of (pro) renin receptor gene polymorphisms with lacunar infarction and left ventricular hypertrophy in Japanese women : the Ohasama study (2011)
  • Author(s): Hirose T, Totsune K, et al
  • Journal Title: Hypertens Res Volume: 34 Pages: 530-535
  • NAID: 10031163212
  • Peer Reviewed
• [Journal Article] Aldosterone-to-renin ratio and nocturnal blood pressure decline in a general population : the Ohasama study (2011)
  • Author(s): Satoh M, Totsune K, et al
  • Journal Title: J Hypertens Volume: 29 Pages: 1940-1947
  • Peer Reviewed
• [Journal Article] Adrenomedullin 2/intermedin in the hypothalamo-pituitary-adrenal axis (2011)
  • Author(s): Takahashi K, Morimoto R, Hirose T, Satoh F, Totsune K
  • Journal Title: J Mol Neurosci Volume: 43 Pages: 182-192
  • Peer Reviewed
• [Journal Article] Expression of kisspeptins and kisspeptin receptor in the kidney of chronic renal failure rats (2010)
  • Author(s): Shoji I, Hirose T, Mori N, Hiraishi K, Kato I, Shibasaki A, Yamamoto H, Ohba K, Kaneko K, Morimoto R, Satoh F, Kohzuki M, Totsune K, Takahashi K.
  • Journal Title: Peptides Volume: Vol.31 Pages: 1920-1925
  • Peer Reviewed
• [Journal Article] Expression of adrenomedullin 2/intermedin, a possible reno-protective peptide, is decreased in the kidneys of rats with hypertension or renal failure (2010)
  • Author(s): Hirose T, Totsune K, Mori N, Mori T, Morimoto R, Metoki H, Asayama K, Kikuya M, Ohkubo T, Kohzuki M, Takahashi K, Imai Y.
  • Journal Title: Am J Physiol Renal Physiol Volume: Vol.299
  • Peer Reviewed
• [Journal Article] Expression of(pro) renin receptor in human kidneys with end-stage kidney disease due to diabetic nephropathy (2010)
  • Author(s): Takahashi K, Yamamoto H, Hirose T, Hiraishi K, Shoji I, Shibasaki A, Kato I, Kaneko K, Sasano H, Satoh F, Totsune K.
  • Journal Title: Peptides Volume: Vol.31 Pages: 1405-1408
  • Peer Reviewed
• [Journal Article] Expression of(pro) renin receptor in the human brain and pituitary, and co-localisation with arginine vasopressin and oxytocin in the hypothalamus (2010)
  • Author(s): Takahashi K, Hiraishi K, Hirose T, Kato I, Yamamoto H, Shoji I, Shibasaki A, Kaneko K, Satoh F, Totsune K.
  • Journal Title: J Neuroendocrinol Volume: Vol.22 Pages: 453-459
  • Peer Reviewed
• [Journal Article] Increased expression of(pro) renin receptor in the remnant kidneys of 5/6 nephrectomized rats (2010)
  • Author(s): Hirose T, Mori N, Totsune K, Morimoto R, Maejima T, Kawamura T, Metoki H, Asayama K, Kikuya M, Ohkubo T, Kohzuki M, Takahashi K, Imai Y.
  • Journal Title: Regul Pept Volume: Vol.159 Pages: 93-99
  • Peer Reviewed
• [Journal Article] Presence of kisspeptin-like immunoreactivity in human adrenal glands and adrenal tumors (2010)
  • Author(s): Takahashi K, Shoji I, Shibasaki A, Kato I, Hiraishi K, Yamamoto H, Kaneko K, Murakami O, Morimoto R, Satoh F, Ito S, Totsune K.
  • Journal Title: J Mol Neurosci Volume: Vol.41 Pages: 138-144
  • Peer Reviewed
• [Journal Article] Expression of (pro)renin receptor in the human brain and pituitary, and co-localisation with arginine vasopressin and oxytocin in the hypothalamus (2010)
  • Author(s): Takahashi K, Hiraishi K, Hirose T, Kato I, Yamamoto H, Shoji I, Shibasaki A, Kaneko K, Satoh F, Totsune K
  • Journal Title: J Neuroendocrinol Volume: 22 Pages: 453-459
  • Peer Reviewed
• [Journal Article] Expression of (pro)renin receptor in human kidneys with end-stage kidney disease due to diabetic nephropathy (2010)
  • Author(s): Takahashi K, Yamamoto H, Hirose T, Hiraishi K, Shoji I, Shibasaki A, Kato I, Kaneko K, Sasano H, Satoh F, Totsune K
  • Journal Title: Peptides Volume: 31 Pages: 1405-1408
  • Peer Reviewed
• [Journal Article] Increased expression of (pro) renin receptor in the remnant kidneys of 5/6 nephrectomized rats. (2010)
  • Author(s): Hirose T, Mori N, Totsune K, Morimoto R, Maejima T, Kawamura T, Metoki H, Asayama K, Kikuya M, Ohkubo T, Kohzuki M, Takahashi K, Imai Y.
  • Journal Title: Regul Pept. 159 Pages: 272-277
  • Peer Reviewed
• [Journal Article] Gene expression of(pro) renin receptor is upregulated in hearts and kidneys of rats with congestive heart failure (2009)
  • Author(s): Hirose T, Mori N, Totsune K, Morimoto R, Maejima T, Kawamura T, Metoki H, Asayama K, Kikuya M, Ohkubo T, Kohzuki M, Takahashi K, Imai Y.
  • Journal Title: Peptides Volume: Vol.30 Pages: 2316-2322
  • Peer Reviewed
• [Journal Article] The renin-angiotensin system, adreno-medullins and urotensin II in the kidney : possible renoprotection via the kidney peptide systems (2009)
  • Author(s): Takahashi K, Hirose T, Mori N, Morimoto R, Kohzuki M, Imai Y, Totsune K.
  • Journal Title: Peptides Volume: Vol.30 Pages: 1575-1585
  • Peer Reviewed
• [Journal Article] Association of (pro) renin receptor gene polymorphism with blood pressure in Japanese men : the Ohasama study. (2009)
  • Author(s): Hirose T, Hashimoto M, Totsune K, Metoki H, Asayama K, Kikuya M, Sugimoto K, Katsuya T, Ohkubo T, Hashimoto J, Rakugi H, Takahashi K, Imai Y.
  • Journal Title: Am J Hypertens 22 Pages: 294-299
  • Peer Reviewed
• [Journal Article] Stroke risk of blood pressure indices determined by home blood pressure measurement : the Ohasama study. (2009)
  • Author(s): Inoue R, Ohkubo T, Kikuya M, Metoki H, Asayama K, Kanno A, Obara T, Hirose T, Hara A, Hoshi H, Totsune K, Satoh H, Kondo Y, Imai Y.
  • Journal Title: Stroke 40 Pages: 2859-2861
  • Peer Reviewed
• [Journal Article] Gene expression of (pro) renin receptor is upregulated in hearts and kidneys of rats with congestive heart failure. (2009)
  • Author(s): Hirose T, Mori N, Totsune K, Morimoto R, Maejima T, Kawamura T, Metoki H, Asayama K, Kikuya M, Ohkubo T, Kohzuki M, Takahashi K, Imai Y.
  • Journal Title: Peptides 30 Pages: 2316-2322
  • Peer Reviewed
• [Presentation] Expression of(pro) renin receptor in human erythroid cell lines : the effect of interferon-gamma (2011)
  • Author(s): Kaneko K, Shibasaki A, Nishiyama H, Hirose T, Ohba K, Totsune K, Furuyama K, Takahashi K.
  • Organizer: 53rd American Society of Hematology(ASH) Annual Meeting and Expositio
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2011-12-12
• [Presentation] (Pro) renin receptor-like immunoreactivity in human plasma (2011)
  • Author(s): Totsune K, Hirose T, Metoki H, Asayama K, Kikuya M, Murakami O, Imai Y, Takahashi K.
  • Organizer: The American Society of Nephrology(ASN), 44th Annual Meeting
  • Place of Presentation: Philadelphia, PA
  • Year and Date: 2011-11-12
• [Presentation] (Pro) renin Receptor-Like Immunoreactivity in Patients with Chronic Renal Failure (2011)
  • Author(s): Kazuhito Totsune, 他7名
  • Organizer: Kidney Week 2011(第44回米国腎臓学会)
  • Place of Presentation: 米国・フィラデルフィア市ペンシルベニアコンベンションセンター
  • Year and Date: 2011-11-12
• [Presentation] アルドステロン産生副腎皮質腺腫と付随副腎における(プロ)レニン受容体の発現 (2011)
  • Author(s): 山本肇、森本玲、加藤一郎、廣瀬卓男、大場浩史、金子桐子、佐藤文俊、戸恒和人、高橋和広
  • Organizer: 第34回日本高血圧学会総会
  • Place of Presentation: 宇都宮
  • Year and Date: 2011-10-21
• [Presentation] 腎ネフロンセグメントにおける(プロ)レニン受容体の発現:高食塩水と脱水による調節Expression of(pro) renin receptor in the nephron segments of rat kidney : Regulation by high salt diet and dehydration (2011)
  • Author(s): 戎栄、伊藤修、森伸芳、森建史、伊藤貞嘉、戸恒和人、高橋和広、上月正博
  • Organizer: 第34回日本高血圧学会総会
  • Place of Presentation: 宇都宮
  • Year and Date: 2011-10-21
• [Presentation] Prorenin receptor, primary aldosteronism and chronic kidney disease : Possible involvement of adrenal prorenin receptor in chronic kidney disease (2011)
  • Author(s): Takahashi K, Yamamoto H, Kato I, Shibasaki A, Ohba K, Kaneko K, Morimoto R, Murakami O, Satoh F, Hirose T, Totsune K.
  • Organizer: 48th Congress of European Renal Association(ERA)-European Dialysis and Transplant Association
  • Place of Presentation: Prague, Czech Republic
  • Year and Date: 2011-06-25
• [Presentation] 血漿・尿中(プロ)レニン受容体可溶性成分の検討 (2011)
  • Author(s): 廣瀬卓男、戸恒和人、森信芳、菊谷昌浩、大久保孝義、高橋和広、今井潤
  • Organizer: 第40回日本心脈管作動物質学会
  • Place of Presentation: 高松
  • Year and Date: 2011-02-04
• [Presentation] Association of (pro)renin receptor gene polymorphism with cardiac hypertrophy, asymptomatic cerebrovascular lesions and chronic kidney disease in Japanese : the Ohasama study (2010)
  • Author(s): Kazuhito Totsune, 他7名
  • Organizer: Renal Week 2010(第43回米国腎臓学会)
  • Place of Presentation: 米国・デンバー市コロラドコンベンションセンター
  • Year and Date: 2010-11-20
• [Presentation] Association of(pro) renin receptor gene polymorphism with cardiac hypertrophy, asymptomatic cerebrovascular lesions and chronic kidney disease in Japanese : the Ohasama study (2010)
  • Author(s): Totsune K, Hirose T, Metoki H, Asayama K, Kikuya M, Ohkubo T, Takahashi K, Imai Y.
  • Organizer: The American Society of Nephrology(ASN), 43rd Annual Meeting
  • Place of Presentation: Denver, USA
  • Year and Date: 2010-09-20
• [Presentation] Association of adrenomedullin 2 gene I/D polymorphism with cerebral and renal damage in a Japanese general population : the Ohasama study (2010)
  • Author(s): Totsune K, Hirose T, Metoki H, Asayama K, Kikuya M, Ohkubo T, Takahashi K, Imai Y.
  • Organizer: The American Society of Nephrology(ASN), 43rd Annual Meeting
  • Place of Presentation: Denver, USA
  • Year and Date: 2010-09-20
• [Presentation] Prorenin receptor in the human brain and pituitary, and its increased expression in the brain of spontaneous hypertensive rats (2010)
  • Author(s): Takahashi K, Hirose T, Hiraishi K, Kato I, Shoji I, Yamamoto H, Shibasaki A, Kaneko K, Mori N, Kohzuki M, Totsune K.
  • Organizer: The 7th International Congress of Neuroendocrinology
  • Place of Presentation: Rouen, France
  • Year and Date: 2010-07-13
• [Presentation] Soluble form of the(Pro) renin receptor in plasma (2010)
  • Author(s): Mori N, Hirose T, Totsune K, Xu B, Rong R, Ito D, Takashima K, Muroya Y, Suzuki F, Nagasaka M, Ebihara S, Ito O, Takahashi K, Imai Y, Kohzuki M.
  • Organizer: 14th International Congress of Endocrinology
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-03-28
• [Presentation] Association of adrenomedullin2/intermedin gene insertion/deletion polymorphism with blood pressure, renal function and silent cerebrovascular lesions in a Japanese general population : the Ohasama study (2010)
  • Author(s): Hirose T, Totsune K, Metoki H, Kawamura T, Hara A, Asayama K, Kondo T, Kikuya M, Ohkubo T, Izumi S-I, Takahashi K, Imai Y.
  • Organizer: 14th International Congress of Endocrinology
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-03-27
• [Presentation] Prorenin receptor expression in the human kidney and brain (2010)
  • Author(s): Takahashi K, Yamamoto H, Hirose T, Hiraishi K, Shoji I, Shibasaki A, Kato I, Kaneko K, Murakami O, Satoh F, Sasano H, Totsune K.
  • Organizer: 14th International Congress of Endocrinology
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2010-03-27
• [Presentation] Expression of prorenin receptor in the human brain and co-localization with arginine vasopression and oxytocin in the hypothalamus (2010)
  • Author(s): Hiraishi K, Hirose T, Yamamoto H, Shoji I, Shibasaki A, Kato I, Kaneko K, Satoh F, Totsune K, Takahashi K.
  • Organizer: 14th International Congress of Endocrinology(ICE2010)
  • Place of Presentation: Sendai, Japan
  • Year and Date: 2010-03-24
• [Presentation] Expression of(pro) renin receptor in the nephron segments of rat kidney : regulation by dehydration (2010)
  • Author(s): Rong R, Mori N, Ito O, Muroya Y, Mori T, Ito S, Totsune K, Takahashi K, Kohzuki M.
  • Organizer: 14th International Congress of Endocrinology(ICE2010)
  • Place of Presentation: Sendai, Japan
  • Year and Date: 2010-03-24
• [Presentation] Renal expression of(Pro) renin receptor is upregulated in rats with chronic renal failure (2009)
  • Author(s): Totsune K, Hirose T, Mori N, Metoki H, Asayama K, Kikuya M, Ohkubo T, Takahashi K, Imai Y.
  • Organizer: The American Society of Nephrology(ASN), 42nd Annual Meeting
  • Place of Presentation: San Diego, USA
  • Year and Date: 2009-10-29
• [Presentation] Renal expression of (Pro) renin receptor is upregulated in rats with chronic renal failure. (2009)
  • Author(s): Kazuhito Totsune, 他8名
  • Organizer: Renal Week 2009(第42回米国腎臓学会)
  • Place of Presentation: 米国・サンディエゴ市
  • Year and Date: 2009-10-29
• [Presentation] アドレノメデュリン2/インターメジン遺伝子多型と無症候性脳血管障害との関連の検討:大迫研究 (2009)
  • Author(s): 廣瀬卓男、戸恒和人、川村卓也、目時弘仁、星川美奈子、原梓、小原拓、浅山敬、菊谷昌浩、近藤健男、大久保孝義、出江紳一、高橋和広、今井潤
  • Organizer: 第32回日本高血圧学会総会
  • Place of Presentation: 大津
  • Year and Date: 2009-10-02