Role of AT4/IRAP extracted by systemic transcriptome analysis for hypertensive and diabetic renal tissue

• Project/Area Number: 22590909
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: University of Fukui
• Principal Investigator: KONOSHITA Tadashi 福井大学, 医学部, 准教授 (40270954)
• Research Collaborator: SUZUKI Jinya 福井大学, 医学部, 助教 (20293417) ; ARAKAWA Kenichiro 福井大学, 医学部, 助教 (80401967) ; ZENIMARU Yasuo 福井大学, 医学部附属病院, 医員 (20397269) ; FUJII Miki 福井大学, 医学部附属病院, 医員 (10401978) ; IMAGAWA Michiko 福井大学, 医学部附属病院, 医員 (70464055) ; ICHIKAWA Mai 福井大学, 医学部附属病院, 医員 (30646659) ; YAMADA Mika 福井大学, 医学部附属病院, 医員 (90646655) ; MAKINO Yasukazu 福井大学, 医学部, 大学院生
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: レニン-アンジオテンシン系 / 網羅的発現遺伝子解析 / AT4/IRAP / 高血圧 / 糖尿病 / 腎臓 / インスリン / アミノペプチダーゼ / ＡＴ４／ＩＲＡＰ

Research Abstract

We have identified AT4/IRAP as a hypertension/diabetes-specific gene through systemic transcriptome analysis followed by RT-PCR. This protein is thought to be involved in the renin-angiotensin system and insulin signal transduction. We have established a measurement system by ELISA. Thereby for the first time we could suggest the possibility that AT4/IRAP might be involved in the pathophysiology of life-style related diseases.

Research Products

• [Journal Article] the Genomic Disease Outcome Consortium (G-DOC) Study Investigators, A crossover comparison of urinary albumin excretion as a new surrogate marker for cardiovascular disease among 4 types calcium channel blockers (2013)
  • Author(s): T. Konoshita, Y. Makino, T. Kimura, M. Fujii, N. Morikawa, S. Wakahara, K. Arakawa, I. Inoki, H. Nakamura, I. Miyamori
  • Journal Title: Int J Cardiol Volume: 166 Pages: 488-452
• [Journal Article] Increased systemic inflammatory interleukin-1s and interleukin-6 during agitation as predictors of Alzheimer's disease. (2013)
  • Author(s): T. Honma, K. Hatta, Y. Hitomi, Y. Kambayashi, Y. Hibino, T. Konoshita, H. Nakamura
  • Journal Title: Int J Geriatr Psychiatry Volume: 28 Pages: 233-241
• [Journal Article] Situs inversus and cystic kidney disease: Two adult patients with this heterogeneous syndrome (2013)
  • Author(s): T. Onoe, T. Konoshita, K. Tsuneyama, R. Hamano, I. Mizushima, Y. Kakuchi, K. Yamada, K. Hayashi, M. Kuroda, S. Kagitani, H. Nomura, M. Yamagishi, M. Kawano
  • Journal Title: Am J Case Rep Volume: 14 Pages: 20-25
  • NAID: 120006319210
• [Journal Article] Decreased activity of daily living produced by the combination of Alzheimer's disease and lower limb fracture in elderly requiring nursing care (2013)
  • Author(s): T. Inagawa, T. Hamagishi, Y. Takaso, Y. Hitomi, Y. Kambayashi, Y. Hibino, A. Shibata, NT. Ngoc, J. Okochi, K. Hatta, K. Takamuku, T. Konoshita, H. Nakamura
  • Journal Title: Environ Health Prev Med Volume: 18 Pages: 16-23
  • NAID: 10031143687
• [Journal Article] Decreased activity of daily living produced by the combination of Alzheimer's disease and lower limb fracture in elderly requiring nursing care. (2013)
  • Author(s): Inagawa T, Konoshita T et al.
  • Journal Title: Environ Health Prev Med Volume: 18 Issue: 1 Pages: 16-23
  • DOI: 10.1007/s12199-012-0283-9
  • NAID: 10031143687
  • Peer Reviewed
• [Journal Article] Situs inversus and cystic kidney disease: Two adult patients with this heterogeneous syndrome. (2013)
  • Author(s): Onoe T, Konoshita T et al.
  • Journal Title: Am J Case Rep Volume: 14 Pages: 20-25
  • DOI: 10.12659/ajcr.883751
  • NAID: 120006319210
  • Peer Reviewed
• [Journal Article] Increased systemic inflammatory interleukin-1β and interleukin-6 during agitation as predictors of Alzheimer's disease. (2013)
  • Author(s): Honma T, Konoshita T et al.
  • Journal Title: Int J Geriatr Psychiatry Volume: 28 Issue: 3 Pages: 233-241
  • DOI: 10.1002/gps.3816
  • Peer Reviewed
• [Journal Article] Differential effects of α-glucosidase inhibitors on postprandial plasma glucose and lipid profile in patients with type 2 diabetes under control with insulin lispro mix 50/50 (2012)
  • Author(s): T. Kimura, J. Suzuki, M. Ichikawa, M. Imagawa, S. Sato, M. Fujii, Y. Zenimaru, S. Inaba, S. Takahashi, T. Konoshita, I. Miyamori
  • Journal Title: Diabetes Technol Ther Volume: 14 Pages: 545-551
• [Journal Article] Aldosterone inhibits endothelial morphogenesis and angiogenesis through the downregulation of vascular endothelial growth factor receptor-2 expression subsequent to peroxisome proliferator-activated receptor gamma (2012)
  • Author(s): M. Fujii, I. Inoki, M. Saga, N. Morikawa, KI. Arakawa, S. Inaba, K. Yoshioka, T. Konoshita, I. Miyamori
  • Journal Title: J Steroid Biochem Mol Biol Volume: 129 Pages: 145-152
• [Journal Article] Aldosterone inhibits endothelial morphogenesis and angiogenesis through the downregulation of vascular endothelial growth factor receptor-2 expression subsequent to peroxisome proliferator-activated receptor gamma. (2012)
  • Author(s): Fujii M, Konoshita T et al.
  • Journal Title: J Steroid Biochem Mol Biol Volume: 129 Issue: 3-5 Pages: 145-152
  • DOI: 10.1016/j.jsbmb.2011.12.014
  • Peer Reviewed
• [Journal Article] Differential effects of α-glucosidase inhibitors on postprandial plasma glucose and lipid profile in patients with type 2 diabetes under control with insulin lispro mix 50/50. (2012)
  • Author(s): Kimura T, Konoshita T et al.
  • Journal Title: Diabetes Technol Ther Volume: 14 Issue: 7 Pages: 545-551
  • DOI: 10.1089/dia.2012.0015
  • Peer Reviewed
• [Journal Article] 「高血圧管理とバイオマーカー」５.レニン・アンジオテンシン・アルドステロン系 (2012)
  • Author(s): 此下忠志他
  • Journal Title: 血圧 Volume: 19 Pages: 38-41
• [Journal Article] 「連携して診る腎疾患」12. 降圧薬の選択と降圧目標値－どの降圧薬でどれくらい血圧を下げるのか？－ (2012)
  • Author(s): 此下忠志，山田実夏，市川麻衣
  • Journal Title: medicina Volume: 49 Pages: 1908-1911
• [Journal Article] Do genetic variants of the Renin Angiotensin system predict blood pressure response to Renin-Angiotensin system-blocking drugs? : A systematic review for pharmacogenomics in the Renin Angiotensin system (2011)
  • Author(s): Konoshita T, et al
  • Journal Title: Curr Hypertens Rep Volume: 13 Issue: 5 Pages: 356-361
  • DOI: 10.1007/s11906-011-0212-0
• [Journal Article] A new generation N/L type calcium channel blocker leads to less activation of the renin-angiotensin system compared with conventional L type calcium channel blocker (2010)
  • Author(s): T. Konoshita, Y. Makino, T. Kimura, M. Fujii, S. Wakahara, K. Arakawa, I. Inoki, H. Nakamura, I. Miyamori I and the Genomic Disease Outcome Consortium (G-DOC) Study Investigators
  • Journal Title: J Hypertens Volume: 28 Pages: 2156-2160
• [Journal Article] A new generation N/L type calcium channel blocker leads to less activation of the renin-angiotensin system compared with conventional L type calcium blocker. (2010)
  • Author(s): Konoshita T, Makino Y, et al.
  • Journal Title: J Hypertens Volume: 28 Pages: 2156-2160
  • Peer Reviewed
• [Presentation] RASにおけるファルマコジェネティクスとバイオマーカーとしての可能性 (2012)
  • Author(s): 此下忠志, 他
  • Organizer: 第3回東京レニンアンジオテンシン研究会
  • Place of Presentation: 東京(招待講演)
  • Year and Date: 2012-01-21
• [Presentation] Systemic transcriptome analysis for extraction of specific gene clusters in diabetic nephropathy-reduced expression of insulin regulated aminopeptidase angiotensin IV receptor (AT4/IRAP) in diabetic renal tissue (2012)
  • Author(s): T. Konoshita, M. Ichikawa, T. Kimura, S. Sato, M. Fujii, Y. Makino, S. Wakahara, I. Miyamori
  • Organizer: 49th Congress of European Renal Association-European Dialysis and Transplant Association
  • Place of Presentation: Paris, France
• [Presentation] A systematic review of pharmacogenetics in the renin angiotensin system - The genetic variants and inter-individual variation in blood pressure response to the blocking agents (2012)
  • Author(s): T. Konoshita, T. Kimura, M. Fujii, Y. Makino, S. Wakahara, I. Miyamori, N. Kato
  • Organizer: 22nd European Meeting on Hypertension
  • Place of Presentation: London, UK
• [Presentation] A systematic review of pharmacogenetics in the renin angiotensin system- The genetic variants and inter-individual variation in blood pressure response to the blocking agents. (2012)
  • Author(s): Konoshita T et al.
  • Organizer: 22nd European Meeting on Hypertension
  • Place of Presentation: London（England of the United Kingdom）
• [Presentation] Systemic transcriptome analysis for extraction of specific gene clusters in diabetic nephropathy-reduced expression of insulin regulated aminopeptidase angiotensin IV receptor (AT4/IRAP) in diabetic renal tissue-. (2012)
  • Author(s): Konoshita T et al.
  • Organizer: 49th Congress of European Renal Association-European Dialysis and Transplant Association
  • Place of Presentation: Paris（France）
• [Presentation] 地域コホート研究，G-DOC Studyの取り組み (2012)
  • Author(s): 此下忠志他
  • Organizer: 第１回臨床高血圧フォーラム
  • Place of Presentation: 大阪
• [Presentation] 治療抵抗性高血圧の予測因子 -糖尿病合併高血圧診療の実際とRA系遺伝子型- (2012)
  • Author(s): 此下忠志
  • Organizer: 第1回治療抵抗性高血圧フォーラム
  • Place of Presentation: 仙台
• [Presentation] 糖尿病と腎症について-糖尿病合併高血圧診療の実際とRA系遺伝子型-，腎機能から診る糖尿病 (2012)
  • Author(s): 此下忠志
  • Organizer: 腎機能から診る糖尿病治療カンファレンス
  • Place of Presentation: 福井
• [Presentation] 高血圧診療における最新の薬剤選択法と降圧目標 (2012)
  • Author(s): 此下忠志
  • Organizer: Hypertension Meeting in Kanazawa
  • Place of Presentation: 金沢
• [Presentation] 尿酸代謝とレニン-アンジオテンシン系 (2011)
  • Author(s): 此下忠志, 他
  • Organizer: 第15回日本心血管内分泌代謝学会
  • Place of Presentation: 大阪
  • Year and Date: 2011-11-25
• [Presentation] 転写調節、網羅的発現遺伝子解析からみたレニン-アンジオテンシン系 (2011)
  • Author(s): 此下忠志, 他
  • Organizer: 第15回腎とレニンアンジオテンシン研究会
  • Place of Presentation: 東京(招待講演)
  • Year and Date: 2011-11-18
• [Presentation] 網羅的発現遺伝子解析により抽出された高血圧特異的遺伝子クラスター-高血圧とアンジオテンシン II 消去系遺伝子群発現低下との関連- (2011)
  • Author(s): 此下忠志,加藤規弘,宮森 勇
  • Organizer: 第34回日本高血圧学会
  • Place of Presentation: 宇都宮
  • Year and Date: 2011-10-22
• [Presentation] 網羅的発現遺伝子解析により抽出された高血圧特異的遺伝子クラスター-高血圧とアンジオテンシンII消去系遺伝子群発現低下との関連- (2011)
  • Author(s): 此下忠志, 他
  • Organizer: 第34回日本高血圧学会
  • Place of Presentation: 宇都宮
  • Year and Date: 2011-10-22
• [Presentation] パネルディスカッション1レニン-アンジオテンシン系(RAS)遺伝子型は同系抑制薬の効果を予測し得るか?-RASファルマコジェノミクスのシステマティックレビュー- (2011)
  • Author(s): 此下忠志, 他
  • Organizer: 第34回日本高血圧学会
  • Place of Presentation: 宇都宮
  • Year and Date: 2011-10-20
• [Presentation] 高血圧Up-to Date 3バイオマーカーとリスクの層別化レニン-アンジオテンシン-アルドステロン系 (2011)
  • Author(s): 此下忠志, 他
  • Organizer: 第34回日本高血圧学会
  • Place of Presentation: 宇都宮
  • Year and Date: 2011-10-20
• [Presentation] 網羅的解析による高血圧特異的発現遺伝子の抽出-RAS 抑制系遺伝子群の意義- (2011)
  • Author(s): 此下忠志,加藤規弘,宮森 勇
  • Organizer: 第84回日本内分泌学会学術総会
  • Place of Presentation: 神戸
  • Year and Date: 2011-04-23
• [Presentation] 網羅的解析による高血圧特異的発現遺伝子の抽出-RAS抑制系遺伝子群の意義 (2011)
  • Author(s): 此下忠志, 他
  • Organizer: 第84回日本内分泌学会学術総会
  • Place of Presentation: 神戸
  • Year and Date: 2011-04-23
• [Presentation] 網羅的解析による高血圧特異的発現遺伝子の抽出-RAS抑制系遺伝子の意義- (2011)
  • Author(s): 此下忠志
  • Organizer: 第31回関東腎研究会
  • Place of Presentation: 東京 招待講演
  • Year and Date: 2011-01-22
• [Presentation] A proximal direct repeat motif characterized as a negative regulatory element in the human renin gene. (2011)
  • Author(s): T. Konoshita, Y. Makino, T. Kimura, S. Wakahara, I. Miyamori
  • Organizer: 21th European Meeting on Hypertension
  • Place of Presentation: Milan, Italy
• [Presentation] A Proximal Direct Repeat Motif Characterized as a Negative Regulatory Element in the Human Renin Gene (2011)
  • Author(s): Konoshita T, et al
  • Organizer: 21th European Meeting on Hypertension
  • Place of Presentation: Milan
• [Presentation] メタボリックシンドロームにおけるレニン-アンジオテンシン系亢進-転写調節因子CREB,COUPTFII の意義- (2010)
  • Author(s): 此下忠志,木村朋子,藤井美紀,牧野耕和,荒川健一郎,若原成行,居軒 功,宮森 勇
  • Organizer: 第33回日本高血圧学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2010-10-15
• [Presentation] メタボリックシンドロームにおけるレニン-アンジオテンシン系元進-転写調節因子CREB、COUPTFIIの意義- (2010)
  • Author(s): 此下忠志, 他
  • Organizer: 第33回日本高血圧学会総会
  • Place of Presentation: 福岡
  • Year and Date: 2010-10-15
• [Presentation] G-DOC Study Investigators,網羅的解析による糖尿病腎症特異的発現遺伝子の抽出-Insulin Regulated Aminopeptidase (IRAP/AT4) の発現低下- (2010)
  • Author(s): 此下忠志,加藤規弘,高橋芳徳,水野真一,木村朋子,藤井美紀,牧野耕和,荒川健一郎,若原成行,居軒 功,宮森 勇
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2010-05-29
• [Presentation] 網羅的解析による糖尿病腎症特異的発現遺伝子の抽出-Insulin Regulated Aminopeptidase (IRAP/AT4)の発現低下- (2010)
  • Author(s): 此下忠志, 他
  • Organizer: 第53回日本糖尿病学会年次学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2010-05-29
• [Presentation] Systemic transcriptome analysis for extraction of specific gene clusters in diabetic nephropathy-reduced expression of insulin regulated aminopeptidase angiotensin IV receptor (IRAP/AT4) in diabetic renal tissue (2010)
  • Author(s): T. Konoshita, Y. Takahashi, S. Mizuno, T. Kimura, M. Fujii, Y. Makino, S. Wakahara, K. Arakawa, I. Inoki, I. Miyamori
  • Organizer: 43th Annual Meeting of American Society of Nephrology
  • Place of Presentation: Denver, USA
• [Presentation] The insulin regulated aminopeptidase/ angiotensin IV receptor (IRAP/AT4) gene expression is downregulated in human kidneys with diabetic nephropathy (2010)
  • Author(s): T. Konoshita, N. Kato, Y. Takahashi, S. Mizuno, T. Kimura, M. Fujii, Y. Makino, S. Wakahara, K. Arakawa, I. Inoki, I. Miyamori
  • Organizer: American Diabetes Association 69th scientific sessions
  • Place of Presentation: Orlando, USA
• [Presentation] the Genomic Disease Outcome Consortium (G-DOC) Study Investigators, A cross-over comparison of anti-albuminuric effects among 4 types calcium channel blockers on chronic kidney disease (2010)
  • Author(s): T. Konoshita, Y. Makino, T. Kimura, M. Fujii, S. Wakahara, K. Arakawa, I. Inoki, I. Miyamori
  • Organizer: 20th European Meeting on Hypertension
  • Place of Presentation: Oslo, Norway
• [Presentation] N/L type calcium channel blocker, cilnidipine, leads to less activation of the renin-angiotensin system compared with L type calcium channel blocker, amlodipine besilate (2010)
  • Author(s): T. Konoshita, T. Kimura, Y. Makino, M. Fujii, S. Wakahara, K. Arakawa, I. Inoki, I. Miyamori, the Genomic Disease Outcome Consortium (G-DOC) Study Investigators
  • Organizer: International Society of Nephrology NEXUS Symposium
  • Place of Presentation: Kyoto
• [Presentation] N/L Type Calcium Channel Blocker, Cilnidipine, Leads to Less Activation of the Renin-Angiotensin System Compared with L Type Calcium Channel Blocker, Amlodipine Besilate (2010)
  • Author(s): Konoshita T, et al.
  • Organizer: International Society of Nenhrology NEXUS Symposium
  • Place of Presentation: Kyoto
• [Presentation] A Cross-Over Comparison of Anti-Albuminuric Effects Among 4 Types Calcium Channel Blockers on Chronic Kidney Disease (2010)
  • Author(s): Konoshita T, et al.
  • Organizer: 20th European Meeting on Hypertension
  • Place of Presentation: Oslo
• [Presentation] The Insulin Regulated Aminopeptidase/Angiotensin IV Receptor (IRAP/AT4) Gene Expression is Downregulated in Human Kidneys with Diabetic Nephropathy (2010)
  • Author(s): Konoshita T, Kato N, et al.
  • Organizer: American Diabetes Association 69th scientific sessions
  • Place of Presentation: Orlando
• [Presentation] Systemic Transcriptome Analysis for Extraction of Specific Gene Clusters in Diabetic Nephropathy-Reduced Expression of Insulin Regulated Aminopeptidase Angiotensin IV Receptor (IRAP/AT4) in Diabetic Renal Tissue- (2010)
  • Author(s): Konoshita T, et al.
  • Organizer: 43th. Annual Meeting of American Society of Nephrology
  • Place of Presentation: Denver
• [Book] 糖尿病腎症のすべて (ヴィジュアル 糖尿病臨床のすべて) (2012)
  • Author(s): 此下忠志,佐藤さつき
  • Publisher: 中山書店
• [Book] 糖尿病腎症のすべて (ヴィジュアル 糖尿病臨床のすべて) (2012)
  • Author(s): 此下忠志,藤井美紀
  • Publisher: 中山書店
• [Book] ヴィジュアル 糖尿病臨床のすべて（分担分） (2012)
  • Author(s): 此下忠志，佐藤さつき
  • Total Pages: 244
  • Publisher: 中山書店
• [Book] ヴィジュアル 糖尿病臨床のすべて（分担分） (2012)
  • Author(s): 此下忠志，藤井美紀
  • Total Pages: 244
  • Publisher: 中山書店
• [Book] ガイドライン/ガイダンス CKD (2011)
  • Author(s): 此下忠志
  • Publisher: 日本医事新報社