Exploring the Epigenetic Abnormalities of Mineralocorticoid Receptor Activation in Salt-sensitive Hypertension and Nephropathy

• Project/Area Number: 25860669
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: The University of Tokyo
• Principal Investigator: KAWARAZAKI Wakako 東京大学, 先端科学技術研究センター, 特任研究員 (50424594)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 高血圧症 / 腎臓 / 食塩感受性 / ナトリウム輸送体 / エピジェネティクス / 食塩感受性高血圧 / 肥満 / ミネラロコルチコイド受容体 / アルドステロン / Rac1

Outline of Final Research Achievements

To explore the pathogenesis of salt-sensitive hypertension and kidney injury, which is deeply associated with obesity and intake of excess salt, we investigated the abnormalities of sodium transporter of kidney tubules in salt-sensitive hypertensive rodents. Sympathetic nerves system, renin-angiotensin-aldosterone system and insulin are considered to affect the regulation of sodium absorption in the kidney of obese hypertensive rats, and we found that the involvement of the activation of Na-K-2Cl-cotransporter (NKCC2) might be involved to it as effector. We are investigating how intake of excess salt induces the aberrant activation of NKCC2, and obesity develops hypertension. Furthermore, we plan to clarify that epigenetic abnormalities of NKCC2-associated genes might be involved to it.

Research Products

• [Journal Article] Diabetes Induces Aberrant DNA Methylation in the Proximal Tubules of the Kidney. (2015)
  • Author(s): Marumo T, Yagi S, Kawarazaki W, Nishimoto M, Ayuzawa N, Watanabe A, Ueda K, Hirahashi J, Hishikawa K, Sakurai H, Shiota K, Fujita T.
  • Journal Title: J Am Soc Nephrol. Volume: 印刷中 Issue: 10 Pages: 2333-2397
  • DOI: 10.1681/asn.2014070665
  • Peer Reviewed
• [Journal Article] 食塩と高血圧研究の最前線 (2015)
  • Author(s): 河原崎和歌子、藤田敏郎
  • Journal Title: 実験医学増刊 先制医療 Volume: 33 Pages: 72-78
• [Journal Article] Aberrant Rac1-mineralocorticoid receptor pathways in salt-sensitive hypertension (2013)
  • Author(s): Kawarazaki, W., and Fujita, T
  • Journal Title: Clin Exp Pharmacol Physiol Volume: 40 Issue: 12 Pages: 929-936
  • DOI: 10.1111/1440-1681.12177
  • Peer Reviewed
• [Journal Article] Rac1とRAAS (2013)
  • Author(s): 河原崎和歌子、長瀬美樹
  • Journal Title: Angiotensin Research Volume: 10 Pages: 226-233
• [Journal Article] 生活習慣病とエピジェネティクス (2013)
  • Author(s): 河原崎和歌子、藤田敏郎
  • Journal Title: Nephrology Frontier Volume: 12 Pages: 308-313
• [Journal Article] 腎疾患とエピジェネティクス (2013)
  • Author(s): 河原崎和歌子、藤田敏郎
  • Journal Title: Nephrology Frontier Volume: 12 Pages: 408-413
• [Remarks] 東京大学・先端科学技術研究センター 臨床エピジェネティクス講座
  • URL: http://www.c-epi.rcast.u-tokyo.ac.jp/
• [Remarks] 東京大学先端科学技術研究センター臨床エピジェネティクス講座ホームページ
  • URL: http://www.c-epi.rcast.u-tokyo.ac.jp/