Cardiac myocyte-derived follistatin like 1 protects the kidney after subtotal nephrectomy

• Project/Area Number: 25461105
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Nagoya University
• Principal Investigator: Ohashi Koji 名古屋大学, 医学(系)研究科(研究院), 寄附講座助教 (10595515)
• Co-Investigator(Kenkyū-buntansha): OUCHI Noriyuki 名古屋大学, 大学院医学系研究科, 寄附講座教授 (00595514) ; SHIBATA Rei 名古屋大学, 大学院医学系研究科, 寄附講座准教授 (70343689) ; MUROHARA Toyoaki 名古屋大学, 大学院医学系研究科, 教授 (90299503)
• 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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: Follistatin like 1 / カルディオカイン / 慢性腎臓病 / AMPキナーゼ / 炎症性サイトカイン / 酸化ストレス

Outline of Final Research Achievements

In the present study, we investigated the role of cardiac Follistatin like (Fstl) 1 in a mouse model of subtotal (5/6) nephrectomy. cFstl1-KO mice showed exacerbation of urinary albumin excretion, histological glomerular damage after subtotal nephrectomy compared with control mice. cFstl1-KO mice also exhibited the increased mRNA levels of proinflammatory cytokines and oxidative stress markers in the remnant kidney. Conversely, systemic administration of adenoviral vectors expressing Fstl1 ameliorates these renal damage. In cultured human mesangial cells, FSTL1 protein attenuated TNF-alpha-stimulated expression of proinflammatory cytokines. Treatment of mesangial cells with FSTL1 protein augmented the phosphorylation of AMP-activated protein kinase (AMPK), and inhibition of AMPK activation abrogated the anti-inflammatory effects of FSTL1. These data suggest that Fstl1 functions in cardiorenal communication, and that the lack of Fstl1 production by myocytes promotes renal damage.

Research Products

• [Journal Article] Cardiac myocyte-derived follistatin-like 1 prevents renal injury in a subtotal nephrectomy model (2015)
  • Author(s): Satoko Hayakawa, Koji Ohashi, Rei Shibata, Yoshiyuki Kataoka, Megumi Miyabe, Takashi Enomoto, Yusuke Joki, Yuuki Shimizu, Takahiro Kambara, Yusuke Uemura, Daisuke Yuasa, Hayato Ogawa, Kazuhiro Matsuo, Mizuho Hiramatsu-Ito, Maurice J.B. van den Hoff, Kenneth Walsh, Toyoaki Murohara and Noriyuki Ouchi
  • Journal Title: Journal of American Society of Nephrology Volume: 26 Issue: 3 Pages: 636-646
  • DOI: 10.1681/asn.2014020210
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Cardiac myocyte-derived follistatin-like 1 protects against renal injury (2014)
  • Author(s): 早川智子、大橋浩二、柴田玲、室原豊明、大内乗有
  • Organizer: 2014年 日本循環器学会
  • Place of Presentation: 東京国際フォーラム（東京都千代田区）
• [Presentation] Follistatin-like 1 functions as a cardiokine that plays a protective role in renal injury (2013)
  • Author(s): 早川智子、大橋浩二、柴田玲、室原豊明、大内乗有
  • Organizer: 2013年 アメリカ心臓病学会
  • Place of Presentation: アメリカ、ダラス