Identification of microRNA that regulates renal pathophysiology related to hypoxia and ER stress

2015 Fiscal Year Final Research Report

• Project/Area Number: 25461207
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: The University of Tokyo
• Principal Investigator: Inagi Reiko 東京大学, 医学部附属病院, 准教授 (50232509)
• Co-Investigator(Kenkyū-buntansha): NAGAGU Masaomi 東京大学, 医学部附属病院, 教授 (90311620) ; WADA Takehiko 東京大学, 医学部附属病院, 助教 (90447409) ; OHSE Takamoto 東京大学, 医学部附属病院, 臨床登録医 (10568447)
• Research Collaborator: JO Airi ; MOTONISHI Shuta ; ISHIMOTO Yu ; OKADA Akira
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: エピゲノム / microRNA / 小胞体ストレス / 酸化ストレス / 虚血・再灌流 / SIRT１ / アクチン細胞骨格 / ポドサイト

Outline of Final Research Achievements

We assessed pathophysiological significance of epigenetics, especially microRNA (miR) or SIRT1, in kidney damage.
1) We identified miR-205, whose expression was markedly decreased both under hypoxia-reoxygenation (HR) and endoplasmic reticulum (ER) stress in tubular cells, and demonstrated that miR-205 regulated stress signals induced by HR or ER stress, subsequently tubular pathological phenotypes.
2) Podocyte-specific SIRT1 deficiency showed more severe glomerular/podocyte damages than control groups under oxidative stress conditions both in vivo and in vitro. As a function of SIRT1 in podocytes, we found that SIRT1 deacetylated cortactin for maintenance of actin cytoskeleton. SIRT1 expression in podocytes were significantly upregulated under the oxidative and ER stress conditions. Collectively, SIRT1 regulates the functional state of cortactin by deacetylation, and maintains actin cytoskeleton integrity in podocytes, suggesting a novel non-epigenetic function of SIRT1 in podocytes.

Free Research Field

医歯薬学