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

2015 Fiscal Year Final Research Report

• 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
• 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.

Free Research Field

循環器内科学