The mechanisms of skin fibrosis and calcification in nephrogenic systemic fibrosis

• Project/Area Number: 25461662
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Gunma University
• Principal Investigator: Ishikawa Osamu 群馬大学, 医学(系)研究科(研究院), 教授 (90168188)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 腎性全身性線維症 / 皮膚線維化 / ガドリニウム / 間葉系幹細胞 / エンドセリン / 石灰化

Outline of Final Research Achievements

Nephrogenic systemic fibrosis (NSF) is characterized by systemic fibrosis and abnormal calcification in patients with severe renal dysfunction. It is considered that gadolinium (Gd)-containing contrast agents used for magnetic resonance imaging trigger the development of NSF. However, the causative role of Gd and the mechanism of Gd-induced fibrosis and calcification in NSF are unknown.We conclude that Gd induces proliferation and calcification of human mesenchymal stem cells via enhancement of endothelin-1/endothelin receptor signalling. Our results contribute to understand the pathogenesis of NSF.

Research Products

• [Journal Article] Role of endothelin-1/endothelin receptor signaling in fibrosis and calcification in nephrogenic systemic fibrosis (2014)
  • Author(s): Motegi S, Okada E, Uchiyama A, Yamada K, Ogino S, Yokoyama Y, Takeuchi Y, Monma F, Suzuki T, Ishikawa O
  • Journal Title: Experimental Dermatology Volume: 23 Issue: 9 Pages: 664-669
  • DOI: 10.1111/exd.12500
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Role of Endothelin-1/Endothelin Receptor Signaling in Fibrosis and Calcification in Nephrogenic Systemic Fibrosis (2014)
  • Author(s): Motegi S, Okada E, Uchiyama A, Yamada K, Ogino S, Yokoyama Y, Takeuchi Y, Monma F, Suzuki T, Ishikawa O
  • Organizer: The 39th Annual Meeting of the Japanese Society for Investigative Dermatology
  • Place of Presentation: 大阪
  • Year and Date: 2014-12-12 – 2014-12-14
• [Presentation] Role of endothelin-1/endothelin receptor signaling in fibrosis and calcification in nephrogenic systemic fibrosis (2013)
  • Author(s): Motegi S, Okada E, Uchiyama A, Yamada K, Uehara A, Ogino S, Takeuchi Y, Ishikawa O
  • Organizer: International Investiagtive Dermatology
  • Place of Presentation: Edinburgh