Heightened crescentic glomerulonephritis in immune challenged 129sv mice is TGF-β/SMAD3 dependent

Yong Du, Chun Xie, Sneha Ravikumar, Jacob Orme, Li Li, Xin J. Zhou, Chandra Mohan

Research output: Contribution to journalArticlepeer-review

Abstract

The 129sv mouse strain is particularly sensitive to experimental immune-mediated ne-phritis. Previous studies have indicated that transforming growth factor-β (TGF-β) plays a critical role in both immune modulation and tissue fibrogenesis in various diseases and that its biological activities are exerted via the SMAD family. In this study, we aimed to determine whether TGF-β/SMAD signaling is essential for the development of immune-mediated nephritis in 129sv mice. Relative to C57BL/6J control mice with anti-glomeruli basement membrane (GBM) nephritis, 129sv mice with anti-GBM nephritis exhibited increased renal collagen deposition. Additionally, higher mRNA levels of pro-collagen and collagen IV, higher serum levels of active and total TGF-β1, and increased TGF-β1, TGF-βIIR, and phosphorylated SMAD expression were detected in these mice. Deletion of Smad3 in 129sv mice ameliorated anti-GBM induced nephritis, including crescentic glo-merulonephritis. Collectively, these findings indicate that the heightened experimental nephritis and fibrotic disease in the 129sv strain of mice are regulated by SMAD3, which could be a potential therapeutic target for immune-mediated nephritis.

Original languageEnglish (US)
Article number2059
Pages (from-to)1-11
Number of pages11
JournalInternational journal of molecular sciences
Volume22
Issue number4
DOIs
StatePublished - Feb 2 2021

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Fingerprint Dive into the research topics of 'Heightened crescentic glomerulonephritis in immune challenged 129sv mice is TGF-β/SMAD3 dependent'. Together they form a unique fingerprint.

Cite this