Roles of interleukin-18 and osteopontin in renal fibrosis

• 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
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2012: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
• 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 / 尿細管細胞 / インターロイキン18 / 慢性腎臓病 / タイプIコラーゲン / フイブロネクチン / 腎尿細管細胞

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): Nagao T
  • Journal Title: Nephron Extra Volume: 2 Issue: 1 Pages: 87-103
  • 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 Issue: 4 Pages: F833-F844
  • DOI: 10.1152/ajprenal.00557.2010
  • Peer Reviewed
• [Presentation] エプレレノンは糖尿病モデルマウスの線維化を抑制する (2012)
  • Author(s): 大蔵隆文
  • Organizer: 日本腎臓病学会
  • Place of Presentation: 横浜
• [Presentation] 慢性腎炎患者における血中オステオポンチンと腎線維化 (2012)
  • Author(s): 大蔵隆文
  • Organizer: 日本高血圧学会
  • Place of Presentation: 名古屋
• [Presentation] 高血糖によるオステオポンチンはＭＡＰキナーゼおよびＰＩ３キナーゼを介して誘導される (2012)
  • Author(s): 大蔵隆文
  • Organizer: 日本高血圧学会
  • Place of Presentation: 名古屋
• [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
• [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
• [Presentation] 高血圧性臓器障害の評価と治療 (2011)
  • Author(s): 大蔵隆文
  • Organizer: 日本高血圧学会総会
  • Place of Presentation: 宇都宮
• [Presentation] Interleukin-18 Deficiency Protects Against Aldosterone-Induced Interstitial Fibrosis in the Kidney (2011)
  • Author(s): Tomoaki Nagao, Takafumi Okura, Masanori Jotoku, Jun Irita, Daijiro Enomoto, Ken-ichi Miyoshi, Jitsuo Higaki
  • Organizer: High Blood Pressure Research 2011 Scientific Sessions
  • Place of Presentation: Orland FL, USA
• [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: 日本高血庄学会総会
  • Place of Presentation: 宇都宮