Molecular mechanism of the novel hormone/receptor systems in renal and cardiovascular dysfunction

• Project/Area Number: 19590929
• 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 University
• Principal Investigator: TOTSUNE Kazuhito Tohoku University, 大学院・薬学研究科, 准教授 (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): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2007: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• Keywords: 遺伝子 / 循環器 / 高血圧 / 生理活性因子 / 発現・制御 / 腎障害 / 循環器・高血圧 / 生理活性

Research Abstract

最近発見されたホルモン/受容体系の腎障害・心血管障害における役割を検討した。腎不全・心不全動物モデルにてURP, AM2, (プロ)レニン受容体((P)RR)の発現が心臓または腎臓で変化すること、AM2の遺伝子多型は24hABP及び慢性腎疾患に関係し、(P)RRの遺伝子多型が24hABP、左室肥大、脳ラクナ梗塞と関連することを見いだした。これらホルモン/受容体系が実際に腎障害・心血管障害に関与していることが示された。

Research Products

• [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
• [Journal Article] Increased expression of urotensin II-related peptide and its receptor in kidney with hypertension or renal failure (2009)
  • Author(s): Mori N, Hirose T, Nakayama T, Ito O, Kanazawa M, Imai Y, Kohzuki M, Takahashi K, Totsune K
  • Journal Title: Peptides 30 Pages: 400-408
• [Journal Article] Associatidn 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] Increased expression of urotensin II-related peptide and its receptor in kidney with hypertension or renal failure (2009)
  • Author(s): Mori N, Hirose T, Nakayama T, Ito O, Kanazawa M, Imai Y, Kohzuki M, Takahashi K, Totsune K.
  • Journal Title: Peptides 30 Pages: 400-408
  • Peer Reviewed
• [Journal Article] Day-by-day variability of blood pressure and heart rate at home as a novel predictor of prognosis : the Ohasama study (2008)
  • Author(s): Kikuya M, Ohkubo T, Metoki H, Asayama K, Hara A, Obara T, Inoue R, Hoshi H, Hashimoto J, Totsune K, Satoh H, Imai Y
  • Journal Title: Hypertension 52 Pages: 1045-1050
  • NAID: 120003728008
• [Journal Article] Increased expression of adrenomedullin 2/intermedin in rat hearts with congestive heart failure (2008)
  • Author(s): Hirose T, Totsune K, Mori N, Morimoto R, Hashimoto M, Nakashige Y, Metoki H, Asayama K, Kikuya M, Ohkubo T, Hashimoto J, Sasano H, Kohzuki M, Takahashi K, Imai Y
  • Journal Title: Eur J Heart Fail 10 Pages: 840-849
• [Journal Article] Expression of peptide YY in human brain and pituitary tissues (2008)
  • Author(s): Morimoto R, Satoh F, Murakami O, Totsune K, Saruta M, Suzuki T, Sasano H, Ito S, Takahashi K
  • Journal Title: Nutrition 24 Pages: 878-884
• [Journal Article] Expression of adrenomedullin 2/intermedin in human adrenal tumors and attached non-neoplastic adrenal tissues (2008)
  • Author(s): Morimoto R, Satoh F, Murakami O, Hirose T, Totsune K, Imai Y, Arai Y, Suzuki T, Sasano H, Ito S, Takahashi K
  • Journal Title: J Endocrinol 198 Pages: 175-183
• [Journal Article] Association of microalbuminuria with brachial-ankle pulse wave velocity: the Ohasama study (2008)
  • Author(s): Ishikawa T, Hashimoto J, Morito RH, Hanazawa T, Aikawa T, Hara A, Shintani Y, Metoki H, Inoue R, Asayama K, Kikuya M, Ohkubo T, Totsune K, Hoshi H, Satoh H, Imai Y
  • Journal Title: Am J Hypertens 21 Pages: 413-418
• [Journal Article] Increased gene expression of urotensin II-related peptide in the hearts of rats with congestive heart failure (2008)
  • Author(s): Nakayama T, Hirose T, Totsune K, Mori N, Maruyama Y, Maejima T, Minagawa K, Morimoto R, Asayama K, Kikuya M, Ohkubo T, Hashimoto J, Kohzuki M, Takahashi K, Imai Y
  • Journal Title: Peptides 29 Pages: 801-808
• [Journal Article] Immunolocalization of urotensin II and its receptor in human adrenal tumors and attached non-neoplastic adrenal tissues (2008)
  • Author(s): Morimoto R, Satoh F, Murakami O, Totsune K, Arai Y, Suzuki T, Sasano H, Ito S, Takahashi K
  • Journal Title: Peptides 29 Pages: 873-880
• [Journal Article] Increased expression of adrenomedullin 2/intermedin in rat hearts with congestive heart failure (2008)
  • Author(s): Hirose T, Totsune K, Mori N, Morimoto R, Hashimoto M, Nakashige Y, Metoki H, Asayama K, Kikuya M, Ohkubo T, Hashimoto I, Sasano H, Kohzuki M, Takahashi K, Imai Y.
  • Journal Title: Eur J Heart Fail 10 Pages: 840-849
  • Peer Reviewed
• [Journal Article] Expression of peptide YY in human brain and pituitary tissues (2008)
  • Author(s): Morimoto R, Satoh F, Murakami O, Totsune K, Saruta M, Suzuki T, Sasano H, Ito S, Takahashi K.
  • Journal Title: Nutrition 24 Pages: 878-884
  • Peer Reviewed
• [Journal Article] Expression of adrenomedullin 2/intermedin in human adrenal tumors and attached non-neoplastic adrenal tissues (2008)
  • Author(s): Morimoto R, Satoh F, Murakami O, Hirose T, Totsune K, Imai Y, Arai Y, Suzuki T, Sasano H, Ito S, Takahashi K.
  • Journal Title: J Endocrinol 198 Pages: 175-183
  • Peer Reviewed
• [Journal Article] Increased gene expression of urotensin II-related peptide in the hearts of rats with congestive heart failure. (2008)
  • Author(s): Nakayama T, Hirose T, Totsune K, Mori N, Maruyama Y, Maejima T, Minagawa K, Morimoto R, Asayama K, Kikuya M, Ohkub T, HashimoJ, Kohzuki M, Takabashi K, Imai Y.
  • Journal Title: Peptides 29(Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Immunolocalization of urotensin II and its receptor in human adrenal tumors and attached non-neoplastic adrenal tissues. (2008)
  • Author(s): Morimoto R, Satoh F, Murakami O, Totsune K, Arai Y, Suzuki T, Sasano H, Ito S, Takahashi K.
  • Journal Title: Peptides 29(Epub ahead of print)
  • Peer Reviewed
• [Journal Article] Association of microalbuminuria with brachial-ankle pulse wave velocity: the Ohasama studa. (2008)
  • Author(s): Ishikawa T, Hashimoto J, Morito RH, Hanazawa T, Aikawa T, Hara A, Shintani Y, Metoki H, Inoue R, Asayama K, Kikuya M, Ohkubo T, Totsune K, Hoshi H, Satoh H, Imai Y.
  • Journal Title: Am J Hypertens 21 Pages: 413-418
  • Peer Reviewed
• [Journal Article] Kidney dysfunction as a risk factor for first symptomatic stroke events in a general Japanese population-the Ohasama study (2007)
  • Author(s): Nakayama M, Metoki H, Terawaki H, Ohkubo T, Kikuya M, Sato T, Nakayama K, Asayama K, Inoue R, Hashimoto J, Totsune K, Hoshi H, Ito S, Imai Y
  • Journal Title: Nephrol Dial Transplant 22 Pages: 1910-1915
• [Journal Article] Kidney dysfunction as a risk factor for first symptomatic stroke events in a general Japanese Population-the Ohasama study. (2007)
  • Author(s): Nakayama M, Metoki H, Terawaki H, Ohkubo T, Kikuya M, Sato T, Nakayama K, Asayama K, Inoue R, Hashimoto J, Totsune K, Hoshi H, Ito S, Imai Y.
  • Journal Title: Nephrol Dial Transplant 22 Pages: 1910-1915
  • Peer Reviewed
• [Presentation] Decreased expression of adrenomedullin 2 in the kidney of rats with hypertension or chronic renal failure. The American Society of Nephrology (2008)
  • Author(s): Totsune K, Hirose T, Mori N, Metoki H, Asayama K, Kikuya M, Ohkubo T, Hashimoto J, Takahashi K, Imai Y
  • Organizer: 41^<st> Annual Meeting
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2008-11-08
• [Presentation] Decreased expression of adrenomedullin 2 in the kidney of rats with hypertension or chronic renal failure (2008)
  • Author(s): Totsune K, Hirose T, Mori N, Metoki H, Asayama K, Kikuya M, Ohkubo T, Hashimoto J, Takahashi K, Imai Y.
  • Organizer: The American Society of Nephrology, 41^<st> Annual Meeting
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2008-11-08
• [Presentation] Adrenomedullin 2 gene I/D polymorphism is associated with blood pressure, renal function, and proteinuria in a Japanese general population: the Ohasama study. The American Society of Nephrology (2008)
  • Author(s): Totsune K, Hirose T, Nakashige Y, Metoki H, Asayama K, Kikuya M, Ohkubo T, Hashimoto J, Takahashi K, Imai Y
  • Organizer: 41^<st> Annual Meeting
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2008-11-06
• [Presentation] Adrenomedullin 2 gene I/D polymorphism is associated with blood pressure, renal function, and proteinuria in a Japanese general population : the Ohasama study (2008)
  • Author(s): Totsune K, Hirose T, Nakashige Y, Metoki H, Asayama K, Kikuya M, Ohkubo T, Hashimoto J, Takahashi K. Imai Y.
  • Organizer: The American Society of Nephrology, 41^<st> Annual Meeting
  • Place of Presentation: Philadelphia, USA
  • Year and Date: 2008-11-06
• [Presentation] ヒト副腎腫瘍におけるAdrenomedullin 2/Intermedinの発現 (2008)
  • Author(s): 森本玲、佐藤文俊、村上治、戸恒和人、荒井陽一、鈴木貴、笹野公伸、伊藤貞嘉、高橋和広
  • Organizer: 第31回日本高血圧学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2008-10-09
• [Presentation] (プロ)レニン受容体遺伝子多型と高血圧性臓器障害との関連の検討大迫研究 (2008)
  • Author(s): 廣瀬卓男、橋本和啓、戸恒和人、川村卓也、目時弘仁、浅山敬、菊谷昌浩、大久保孝義、橋本潤一郎、高橋和広、今井潤
  • Organizer: 第31回日本高血圧学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2008-10-09
• [Presentation] ヒト副腎腫瘍におけるAdrenomedullin 2/ Intermedinの発現 (2008)
  • Author(s): 森本鈴、佐藤文俊、村上治、戸恒和人、荒井陽一、鈴木貴、笹野公伸、伊藤貞嘉、高橋和広
  • Organizer: 第31回日本高血圧学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2008-10-09
• [Presentation] (プロ)レニン受容体遺伝子多型と高血圧性臓器障害との関連の検討 : 大迫研究 (2008)
  • Author(s): 廣瀬卓男、橋本和啓、戸恒和人、川村卓也、目時弘仁、浅山敬、菊谷昌浩、大久保孝義、橋本潤一郎、高橋和広、今井潤
  • Organizer: 第31回日本高血圧学会総会
  • Place of Presentation: 札幌
  • Year and Date: 2008-10-09
• [Presentation] Adrenomedullin 2 and cardiovascular and renal systems (2008)
  • Author(s): Totsune K, Hirose T, Takahashi K, Imai Y
  • Organizer: First meeting of the Japan Branch of the International Neuropeptide Society, and Tohoku University 21st Century COE Symposium (CRESCENDO)
  • Place of Presentation: 仙台
  • Year and Date: 2008-09-01
• [Presentation] CKDにおけるAM2遺伝子多型の関与 (2008)
  • Author(s): 戸恒和人、廣瀬卓男、中繁由紀子、浅山敬、丸山穣、藤原正子竹内和久、菊谷昌浩、大久保孝義、橋本潤一郎、高橋和広、今井潤
  • Organizer: 第53回(社)日本透析医学会学術集会・総会
  • Place of Presentation: 神戸
  • Year and Date: 2008-06-20
• [Presentation] ラット腎臓におけるレニン受容体及びレニンの遺伝子発現 : WKY及びSHRでの検討 (2008)
  • Author(s): 廣瀬卓男、戸恒和人、森信芳、橋本和啓、中繁由紀子、丸山穣、浅山敬、菊谷昌浩、大久保孝義、橋本潤一郎、高橋和広、今井潤
  • Organizer: 第51回日本腎臓学会学術総会
  • Place of Presentation: 福岡
  • Year and Date: 2008-06-01
• [Presentation] Adrenomedullin2遺伝子多型とCKDとの関連の検討 (2008)
  • Author(s): 戸恒和人、廣瀬卓男、中繁由紀子、橋本和啓、浅山敬、菊谷昌浩、大久保孝義、橋本潤一郎、高橋和広、今井潤
  • Organizer: 第51回日本腎臓学会学術総会
  • Place of Presentation: 福岡
  • Year and Date: 2008-06-01
• [Presentation] 自然発症高血圧ラットの心臓・腎臓におけるウロテンシンII、ウロテンシンII関連ペプチド、ウロテンシンII受容体の遺伝子発現 (2008)
  • Author(s): 戸恒和人、廣瀬卓男、森信芳、橋本和啓、中繁由紀子、浅山敬、菊谷昌浩、大久保孝義、橋本潤一郎、高橋和広、今井潤
  • Organizer: 第81回日本内分泌学会学術総会
  • Place of Presentation: 青森
  • Year and Date: 2008-05-16
• [Presentation] 心臓におけるAdrenomedullin 2の発現変化心不全ラットでの検討 (2008)
  • Author(s): 廣瀬卓男、戸恒和人、森信芳、中繁由紀子、橋本和啓、浅山敬、菊谷昌浩、大久保孝義、橋本潤一郎、高橋和広、今井潤
  • Organizer: 第81回日本内分泌学会学術総会
  • Place of Presentation: 青森
  • Year and Date: 2008-05-16
• [Presentation] 心臓におけるAdrenomedullin 2の発現変化 : 心不全ラットでの検討 (2008)
  • Author(s): 廣瀬卓男、戸恒和人、森信芳、中繁由紀子、橋本和啓、浅山敬、菊谷昌浩、大久保孝義、橋本潤一郎、高橋和広、今井潤
  • Organizer: 第81回日本内分泌学会学術総会
  • Place of Presentation: 青森
  • Year and Date: 2008-05-16
• [Presentation] Ap 1 and AP-2a synergistically activate the gene promoter of human adrenomedullin, a potent vasodilator peptide (2008)
  • Author(s): Takahashi K, Zhang Y, Li Y.
  • Organizer: 22^<nd> Scientific Meeting of International Society o Hypertension. Hypertension Berlin 2008
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2008-05-16
• [Presentation] Ap 1 and AP-2a synergistically activate the gene promoter of human adrenomedullin, a potent vasodilator peptide (2008)
  • Author(s): Takahashi K, Zhang Y, Li Y
  • Organizer: 22^<nd> Scientific Meeting of International Society of Hypertension. Hypertension Berlin 2008
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2008-05-15
• [Presentation] Expression of adrenomedullin 2/intermedin in human adrenal tumors and attached non-neoplastic adrenal tissues (2008)
  • Author(s): Morimoto R, Satoh F, Murakami O, Hirose T, Totsune K, Imai Y, Arai Y, Suzuki T, Sasano H, Ito S, Takahashi K
  • Organizer: 22^<nd> Scientific Meeting of International Society of Hypertension Hypertension Berlin 2008
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2008-05-14
• [Presentation] Expression of adrenomedullin 2/intermedin in human adrenal tumors and attached non-neoplastic adrenal tissues (2008)
  • Author(s): Morimoto R, Satoh F, Murakami O, Hirose T, Totsune K, Imai Y, Arai Y, Suzuki T, Sasano H, Ito S, Takahashi K.
  • Organizer: 22^<nd> Scientific Meeting of International Society of Hypertension. Hypertension Berlin 2008
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2008-05-14
• [Presentation] Adrenomedullin 2/Intermedin(AM2/IMD)遺伝子多型と高血圧症との関連の検討 (2007)
  • Author(s): 中繁由起子、戸恒和人、廣瀬卓男、橋本和啓、浅山敬、菊谷昌浩、大久保孝義、橋本潤一郎、高橋和広、今井潤
  • Organizer: 第11回日本心血管内分泌代謝学会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-17
• [Presentation] 心不全ラット心臓におけるAdrenomedullin 2/Intermedinの遺伝子発現 (2007)
  • Author(s): 廣瀬卓男、戸恒和人、森信芳、中繁由起子、橋本和啓、菊谷昌浩、大久保孝義、橋本潤一郎、高橋和広、今井潤
  • Organizer: 第11回日本心血管内分泌代謝学会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-17
• [Presentation] Adrenomedullin 2/Intermedin (AM2/IMD)遺伝子多型と高血圧症との関連の検討 (2007)
  • Author(s): 中繁由起子、戸恒和人、廣瀬卓男、橋本和啓、浅山敬、菊谷昌浩、大久保孝義、橋本潤一郎、高橋和広、今井 潤。
  • Organizer: 第11回日本心血管内分泌代謝学会
  • Place of Presentation: 東京
  • Year and Date: 2007-11-17
• [Presentation] Renal gene expression of(pro)renin receptor: Upregulation in rats with chronic renal failure. The American Society of Nephrology (2007)
  • Author(s): Totsune K, Hirose T, Maejima T, Mori N, Maruyama Y, Asayama K, Kikuya M, Ohkubo T, Hashimoto J, Takahashi K, Imai Y
  • Organizer: 40th Annual Meeting
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2007-11-03
• [Presentation] Renal gene expression of (pro) renin receptor: Upregulation in rats with chronic renal failure. (2007)
  • Author(s): Totsune K, Hirose T, Maejima T, Mori N, Maruyama Y, Asayama K, Kikuya M, Ohkubo T, Hashimoto J, Takahashi K, Imai Y
  • Organizer: The American Society of Nephrology, 40th Annual Meeting
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2007-11-03
• [Presentation] 心不全ラットの心臓・腎臓における(プロ)レニン受容体の遺伝子発現 (2007)
  • Author(s): 廣瀬卓男、戸恒和人、森信芳、前嶋隆弘、橋本和啓、中繁由起子、目時弘仁、原梓、森戸里衣子、浅山敬、菊谷昌浩、大久保孝義、橋本潤一郎、上月正博、高橋和広、今井潤
  • Organizer: 第30回日本高血圧学会総会
  • Place of Presentation: 沖縄
  • Year and Date: 2007-10-25
• [Presentation] (プロ)レニン受容体遺伝子多型と高血圧症との関連の検討 : 大迫研究 (2007)
  • Author(s): 橋本和啓、戸恒和人、廣瀬卓男、目時弘仁、渡邊悠美子、中繁由起子、井上隆輔、浅山敬、菊谷昌浩、大久保孝義、橋本潤一郎、高橋和広、今井潤
  • Organizer: 第30回日本高血圧学会総会
  • Place of Presentation: 沖縄
  • Year and Date: 2007-10-25
• [Presentation] (プロ)レニン受容体遺伝子多型と高血圧症との関連の検討:大迫研究 (2007)
  • Author(s): 橋本和啓、戸恒和人、廣瀬卓男、目時弘仁、渡邊悠美子、中繁由起子、井上隆輔、浅山 敬、菊谷昌浩、大久保孝義、橋本潤一郎、高橋和広、今井 潤。
  • Organizer: 第30回日本高血圧学会総会
  • Place of Presentation: 沖縄
  • Year and Date: 2007-10-25