Roles of interleukin-18 and osteopontin in renal fibrosis

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590912
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Ehime University
• Principal Investigator: OKURA Takafumi 愛媛大学, 大学院・医学系研究科, 准教授 (40260385)
• Co-Investigator(Renkei-kenkyūsha): MIYOSHI Ken-ichi 愛媛大学, 大学院・医学系研究科, 助教 (50423439) ; IRITA Jun 愛媛大学, 医学部附属病院, 助教 (00423442) ; JHOTOKU Masanori 愛媛大学, 医学部附属病院, 医員 (10452690) ; NAGAO Tomoaki 愛媛大学, 医学部附属病院, 医員 (20512164)
• Project Period (FY): 2010 – 2012
• Keywords: Interleukin-18 / オステオポンチン / アルドステロン / 腎線維化 / 高血圧

Research Abstract

We evaluated the effects of IL-18 which is a pro-inflammatory cytokine on kidney injury by aldosterone. Wild type or IL-18 knock out (KO) mouse were unilateral nephrectomized and treated with high salt and aldosterone. In wild type mouse, glomerular hypertrophy, mesangial matrix expansion and interstitial fibrosis were observed. On the other hand, in IL-18 KO mouse, these changes were diminished. In wild type mouse, osteopontin (OPN) was up-regulated but not in KO mouse. These results suggested that aldosterone induced renal fibrosis by induction of IL-18 and OPN.

Research Products

• [Journal Article] Osteopontin Plays a Critical Role in Interstitial Fibrosis but Not Glomerular Sclerosis in Diabetic Nephropathy (2012)
  • Author(s): NagaoT, Okura T, Irita J, Jotoku M, Enomoto D, Desilva VR, Miyoshi K, Kurata M, Matsui Y, Uede T, Higaki J
  • Journal Title: Nephron Extra Volume: 2 Pages: 87-103
  • DOI: DOI: 10.1159/000337330
  • Peer Reviewed
• [Journal Article] Osteopontin deficiency protects against aldosterone-induced inflammation, oxidative stress, and interstitial fibrosis in the kidney. (2011)
  • Author(s): Irita J, Okura T, Jotoku M, NagaoT, Enomoto D, Kurata M, Desilva VR, Miyoshi K, Matsui Y, Uede T, Denhardt DT, Rittiling SR, Higaki J.
  • Journal Title: American Journal of Physiology renal physiology Volume: 301 Pages: E833-844
  • DOI: DOI:10.1152/ajprenal.00557.2010
  • Peer Reviewed
• [Presentation] アルドステロンによる腎線維化におけるIL-18 とオステオポンチンの役割 (2011)
  • Author(s): 長尾知明、大蔵隆文、城徳昌典、榎本大次郎、入田 純、三好賢一、檜垣實男
  • Organizer: 第34回日本高血圧学会総会
  • Place of Presentation: 宇都宮
  • Year and Date: 20111020-22
• [Presentation] Interleukin-18 Deficiency Protects Against Aldosterone-Induced Interstitial Fibrosis in the Kidney. (2011)
  • Author(s): Nagao,T Okura T, Jotoku M, Irita J, Enomoto D, Miyoshi K, Higaki J.
  • Organizer: High Blood Pressure Research 2011 Scientific Sessions
  • Place of Presentation: Orland FL, USA
  • Year and Date: 20110920-24