The role of Angiopoietin-like protein 2 in renal fibrosis

• Project/Area Number: 26860639
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: Kumamoto University
• Principal Investigator: Morinaga Jun 熊本大学, その他の研究科, その他 (50459210)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 腎線維化 / ANGPTL2 / TGF-β / 尿細管細胞 / マクロファージ / 慢性腎臓病

Outline of Final Research Achievements

Here, we demonstrate a molecular link between chronic inflammation and tissue fibrosis in chronic kidney disease (CKD) progression. Specifically, we report histological analysis indicating abundant expression of angiopoietin-like protein 2 (ANGPTL2) in renal tubule epithelial cells during progression of renal fibrosis. Analysis of collecting duct cells revealed that TGF-β1 increases ANGPTL2 expression by attenuating its repression by the microRNA-221. Conversely, ANGPTL2 increased TGF-β1 expression through α5β1 integrin-mediated activation of extracellular signal-regulated kinase. Furthermore, ANGPTL2 deficiency in a mouse unilateral ureteral obstruction model significantly reduced renal fibrosis by decreasing TGF-β1 signal amplification in kidney.
Our study provides insight into molecular mechanisms underlying chronic inflammation and tissue fibrosis and identifies targets potentially useful for CKD treatment.

Research Products

• [Journal Article] Angiopoietin-like protein 2 increases renal fibrosis by accelerating transforming growth factor-β signaling in chronic kidney disease. (2016)
  • Author(s): Jun Morinaga, Tsuyoshi Kadomatsu, Keishi Miyata, Motoyoshi Endo, Kazutoyo Terada, Zhe Tian, Taichi Sugizaki, Hiroki Tanigawa, Jiabin Zhao, Shunshun Zhu, Michio Sato, Kimi Araki, Ken-ichi Iyama, Kengo Tomita, Masashi Mukoyama, Kimio Tomita, Kenichiro Kitamura, Yuichi Oike
  • Journal Title: Kidney International Volume: 89 Issue: 2 Pages: 327-341
  • DOI: 10.1016/j.kint.2015.12.021
  • Peer Reviewed
• [Presentation] 腎線維化におけるTGF-βシグナル増幅機構 (2015)
  • Author(s): 森永潤
  • Organizer: 日本腎臓学会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-06-05
• [Presentation] The role of Angiopoietin-like protein 2 in renal fibrosis (2014)
  • Author(s): Jun Morinaga, Rika Yamazoe, Terumasa Nakagawa, Yasuhiro Yoshimura, Yoshikazu Miyasato, Yuki Narita, Yoshihiro Iwashita, Miki Ueda, Teruhiko Mizumoto, Tomoaki Onoue, Kohei Uchimura, Manabu Hayata, Yutaka Kakizoe, Taku Miyoshi, Masataka Adachi, Yuichi Oike, Masashi Mukoyama, Kenichiro Kitamura
  • Organizer: American Society of Nephrology
  • Place of Presentation: Pennsylvania Convention Center
  • Year and Date: 2014-11-11 – 2014-11-16
• [Presentation] ANGPTL2は腎線維化を促進する (2014)
  • Author(s): 森永潤、北村健一郎、冨田公夫、尾池雄一
  • Organizer: 日本腎臓学会学術集会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2014-07-04 – 2014-07-06