An approach to identify novel therapeutics against diabetic nephropathy based on aldosterone synthase gene regulation

• Project/Area Number: 25461381
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: Tohoku University
• Principal Investigator: Sugawara Akira 東北大学, 医学(系)研究科(研究院), 教授 (90270834)
• Co-Investigator(Renkei-kenkyūsha): ITO TAKAKO (SAITO TAKAKO) 東北大学, 病院, 助教 (10375173) ; KUDO MASATAKA 東北大学, 病院, 准教授 (20509583) ; HAKODA AKIKO (SAITO AKIKO) JR仙台病院, 小児科, 医長 (70509398) ; MATSUDA KEN 石巻赤十字病院, 内科, 副部長 (60645935)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: アルドステロン / 糖尿病 / 高血圧 / CYP11B2 / 遺伝子改変マウス / DNAマイクロアレイ / 糖尿病性腎症 / 創薬

Outline of Final Research Achievements

We here have first demonstrated that high glucose (D-glucose) stimulates aldosterone synthase (CYP11B2) gene transcription and mRNA expression via the induction of transcription factor Nurr-1, and results in the increase of aldosterone secretion using human adrenocortical H295R cells. It is therefore suggested that high glucose levels in diabetic patients may promote hypertension, atherosclerosis, and diabetic nephropathy via the induction of aldosterone secretion.

Research Products

• [Journal Article] Hydroxylation of methylated DNA by TET1 in chondrocyte differentiation of C3H10T1/2 cells (2016)
  • Author(s): Ito R, Shimada H, Yazawa K, Sato I, Imai Y, Sugawara A, Yokoyama A
  • Journal Title: Biochem Biophys Rep Volume: 5 Pages: 134-140
  • DOI: 10.1016/j.bbrep.2015.11.009
  • Peer Reviewed / Open Access
• [Journal Article] The roles of histone modifier complexes in tissue-specific transcriptional regulation (2015)
  • Author(s): 横山 敦、菅原 明
  • Journal Title: 生化学 Volume: 87 Issue: 5 Pages: 621-624
  • DOI: 10.14952/SEIKAGAKU.2015.870621
  • NAID: 40020650274
  • ISSN: 0037-1017
  • Year and Date: 2015-10-25
• [Journal Article] Role of Histamine H3 Receptor in Glucagon-Secreting αTC1.6 cells (2015)
  • Author(s): Tadaho Nakamura, Takeo Yoshikawa, Fumito Naganuma, Attyeb Mohsen, Tomomitsu iida, Yamato Miura, Akira Sugawara and Kazuhiko Yanai
  • Journal Title: FEBS Open Bio Volume: 5 Issue: 1 Pages: 36-41
  • DOI: 10.1016/j.fob.2014.12.001
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Effects of RXR agonists on cell proliferation/apoptosis and ACTH secretion/Pomc expression (2015)
  • Author(s): Saito-Hakoda A, Uruno A, Yokoyama A, Shimizu K, Parvin R, Kudo M, Saito-Ito T, Sato I, Kogure N, Suzuki D, Shimada H, Yoshikawa T, Fujiwara I, Kagechika H, Iwasaki Y, Kure S, Ito S, Sugawara A
  • Journal Title: PLoS One Volume: 10 Issue: 12 Pages: e0141960-e0141960
  • DOI: 10.1371/journal.pone.0141960
  • Peer Reviewed / Open Access
• [Journal Article] Retinoic acid receptor-α up-regulates proopiomelanocortin gene expression in AtT20 corticotroph cells. (2014)
  • Author(s): Uruno A, Saito-Hakoda A, Yokoyama A, Kogure N, Matsuda K, Parvin R, Shimizu K, Sato I, Kudo M, Yoshikawa T, Kagechika H, Iwasaki Y, Ito S, Sugawara A.
  • Journal Title: Endocr J. Volume: 61 Pages: 1105-1114
  • NAID: 130004677954
  • Peer Reviewed
• [Journal Article] Identification of myelin transcription factor 1 (MyT1) as a subunit of the neural cell type-specific lysine-specific demethylase 1 (LSD1) complex. (2014)
  • Author(s): Yokoyama A, Igarashi K, Sato T, Takagi K, Otsuka I M, Shishido Y, Baba T, Ito R, Kanno J, Ohkawa Y, Morohashi K, Sugawara A.
  • Journal Title: J Biol Chem. Volume: 289 Issue: 26 Pages: 18152-18162
  • DOI: 10.1074/jbc.m114.566448
  • Peer Reviewed
• [Journal Article] Aberrant gonadotropin-releasing hormone receptor (GnRHR) expression and its regulation of CYP11B2 expression and aldosterone production in adrenal aldosterone-producing adenoma (APA). (2014)
  • Author(s): Nakamura Y, Hattangady NG, Ye P, Satoh F, Morimoto R, Ito-Saito T, Sugawara A, Ohba K, Takahashi K, Rainey WE, Sasano H.
  • Journal Title: Mol Cell Endocrinol. Volume: 384 Issue: 1-2 Pages: 102-108
  • DOI: 10.1016/j.mce.2014.01.016
  • Peer Reviewed
• [Journal Article] PCP4: a regulator of aldosterone synthesis in human adrenocortical tissues. (2014)
  • Author(s): Felizola SJ, Nakamura Y, Ono Y, Kitamura K, Kikuchi K, Onodera Y, Ise K, Takase K, Sugawara A, Hattangady N, Rainey WE, Satoh F, Sasano H.
  • Journal Title: J Mol Endocrinol. Volume: 52 Issue: 2 Pages: 159-167
  • DOI: 10.1530/jme-13-0248
  • Peer Reviewed
• [Journal Article] Angiotensin II receptor blockers differentially affect CYP11B2 expression in human adrenal H295R cells. (2014)
  • Author(s): Matsuda K, Uruno A, Kogure N, Sugawara K, Shimada H, Nezu M, Saito-Ito T, Iki Y, Kudo M, Shimizu K, Sato I, Yoshikawa T, Satoh F, Ito R, Yokoyama A, Rainey WE, Saito-Hakoda A, Ito S, Sugawara A.
  • Journal Title: Mol Cell Endocrinol. Volume: 383(1-2) Issue: 1-2 Pages: 60-68
  • DOI: 10.1016/j.mce.2013.12.004
  • Peer Reviewed
• [Presentation] An approach to identify the undetermined adipocyte-derived factor(s) that stimulate aldosterone synthase gene (CYP11B2) expression (2016)
  • Author(s): Shimada H, Ito R, Sato I, Sato E, Yokoyama A, Sugawara A
  • Organizer: 41st International Aldosterone Conference
  • Place of Presentation: アメリカ合衆国ボストン市
  • Year and Date: 2016-03-30
  • Int'l Joint Research
• [Presentation] Suppressive effects of retinoid X receptor (RXR) agonist PA024 on adrenal CYP11B2 expression, aldosterone secretion, and blood pressure (2016)
  • Author(s): Suzuki D, Saito-Hakoda A, Ito R, Shimizu K, Kogure N, Kagechika H, Kure S, Yokoyama A, Sugawara A
  • Organizer: 41st International Aldosterone Conference
  • Place of Presentation: アメリカ合衆国ボストン市
  • Year and Date: 2016-03-30
  • Int'l Joint Research
• [Presentation] High-glucose stimulates aldosterone synthase gene (CYP11B2) expression via the induction of T-type calcium channels in H295R cells (2014)
  • Author(s): Naotaka Kogure, Ken Matsuda, Akira Uruno, Kaori Sugawara, Ikuko Sato, Kyoko Shimizu, Rehana Parvin, Takeo Yoshikawa Masataka Kudo, Akiko Saito-Hakoda, Ryo Ito, Atsushi Yokoyama, Sadayoshi Ito, Akira Sugawara
  • Organizer: ICE/ENDO2014
  • Place of Presentation: アメリカ合衆国シカゴ
  • Year and Date: 2014-06-23
• [Presentation] The innovation of a novel drug screening system for the inhibitors of aldosterone synthase gene (CYP11B2) expression (2014)
  • Author(s): Ryo Ito, Ken Matsuda, Akira Uruno, Atsushi Yokoyama, Akira Sugawara
  • Organizer: ICE/ENDO2014
  • Place of Presentation: アメリカ合衆国シカゴ
  • Year and Date: 2014-06-23
• [Presentation] Generation of a stable H295R cell line expressing 11-hydroxylase gene promoter and the effect of high-glucose on its expression (2014)
  • Author(s): Kaori Sugawara, Ken Matsuda, Naotaka Kogure, Akira Uruno, Ikuko Sato, Kyoko Shimizu, Rehana Parvin, Takeo Yoshikawa Masataka Kudo, Akiko Saito-Hakoda, Ryo Ito, Atsushi Yokoyama, Sadayoshi Ito, Akira Sugawara
  • Organizer: ICE/ENDO2014
  • Place of Presentation: アメリカ合衆国シカゴ
  • Year and Date: 2014-06-21
• [Book] 今日の診断指針（第7版） (2015)
  • Author(s): 菅原 明
  • Total Pages: 2103
  • Publisher: 医学書院
• [Book] 南山堂医学大辞典（改訂20版） (2015)
  • Author(s): 菅原 明
  • Total Pages: 3101
  • Publisher: 南山堂
• [Remarks] 分子内分泌学分野
  • URL: http://www.med.tohoku.ac.jp/org/health/84/index.html
• [Remarks] Molecular Endocrinology
  • URL: http://www.med.tohoku.ac.jp/english/org/health/84/index.html
• [Remarks] 分子内分泌学分野
  • URL: http://www.med.tohoku.ac.jp/org/health/84/index.html
• [Remarks] Molecular Endocrinology
  • URL: http://www.med.tohoku.ac.jp/english/org/health/84/index.html