Sirt1 and NMN mediate the tubular-PEC crosstalk.

• Project/Area Number: 15K09272
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Keio University
• Principal Investigator: Hasegawa Kazuhiro 慶應義塾大学, 医学部(信濃町), 助教 (30424162)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 近位尿細管 / 糖尿病性腎症 / サーチュイン / ＮＭＮ / ポドサイト / 尿細管糸球体連関 / PEC / Sirt1

Outline of Final Research Achievements

We have recently disclosed that tubular epithelial cells affect the podocyte epigenome though nicotinic acid metabolism in diabetic nephropathy (DN), and we have named this relationship "proximal tubule-podocyte communication". First, we elucidated the details of proximal tubule-podocyte communication. Second, we identified how Sirt1 regulates albuminuria. This means that repeated high glucose stress triggers the initial changes in proximal tubules, which lead to the epigenetically irreversible glomerular damages. Proximal tubular Sirt1 overexpression can rescue these changes. Third, we identified a mediator connecting this communication, nicotinamide mononucleotide (NMN).

Research Products

• [Journal Article] Oral adsorbent AST-120 ameliorates gut environment and protects against the progression of renal impairment in CKD rats. (2018)
  • Author(s): Yoshifuji A, Wakino S, Irie J, Matsui A, Hasegawa K, Tokuyama H, Hayashi K, Itoh H.
  • Journal Title: Clin Exp Nephrol. Volume: 19 Issue: 5 Pages: 1069-1078
  • DOI: 10.1007/s10157-018-1577-z
  • Peer Reviewed
• [Journal Article] Communication from Tubular Epithelial Cells to Podocytes through Sirt1 and Nicotinic Acid Metabolism. (2016)
  • Author(s): Hasegawa K, Wakino S, Sakamaki Y, Kanda T, Tokuyama H, Hayashi K, Itoh H.
  • Journal Title: Curr Hypertens Rev. Volume: 12 Pages: 95-104
  • Peer Reviewed
• [Journal Article] Communication from Tubular Epithelial Cells to Podocytes through Sirt1 and Nicotinic Acid Metabolism (2016)
  • Author(s): Kazuhiro Hasegawa, Shu Wakino, Yusuke Sakamaki, Hirokazu Muraoka, Hiroyuki Umino, Hitoshi Minakuchi, Ayumi Yoshifuji, Makiko Naitoh, Keisuke Shinozuka, Koji Futatsugi, Hidenori Urai, Takeshi Kanda, Hirobumi Tokuyama, Koichi Hayashi and Hiroshi Itoh.
  • Journal Title: Current Hypertension Reviews Volume: 12
  • Peer Reviewed
• [Presentation] 長寿遺伝子を活性化するメソッド：NMN (2016)
  • Author(s): 長谷川一宏、脇野 修、村丘 寛和、海野 寛之、川口 隆久、伊藤 裕
  • Organizer: 第16回 日本抗加齢医学会 総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-06-10
  • Invited
• [Book] Annual Review 2016 腎臓 (2016)
  • Author(s): 長谷川一宏、脇野修、伊藤裕
  • Total Pages: 6
  • Publisher: 中外医学社
• [Remarks] 慶應義塾大学医学部 腎臓内分泌代謝内科 ホームページ 研究活動
  • URL: http://www.keio-emn.jp/research/index.html