Transcription factor Ets-1 is essential for mesangial matrix remodeling

M. Mizui, Y. Isaka, Y. Takabatake, Y. Sato, H. Kawachi, F. Shimizu, S. Takahara, T. Ito, E. Imai

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Most advanced glomerular diseases are characterized by abnormal extracellular matrix (ECM) accumulation in the glomeruli, and matrix metalloproteinases (MMPs) play a pivotal role in ECM remodeling in various glomerular diseases. The proto-oncogene, ets-1, is a transcription factor regulating the expression of various matrix proteinases, including MMP-1, MMP-3, and MMP-9. The goal of the present study was to characterize the role of Ets-1 in the progression of glomerular diseases. Overexpression of Ets-1 in cultured mesangial cells prevented transforming growth factor (TGF)-β-induced inhibition of DNA-binding activity and TGF-β-induced type I collagen production. In addition, exogenous Ets-1 abolished TGF-β-induced collagen gel contraction. The in vivo transfection of the ets-1 gene into nephritic kidney resulted in the increases in glomerular MMP-1, MMP-3, and MMP-9 mRNA, decreases in mesangial ECM deposition, and attenuation of fibronectin extradomain A (EDA) and type I collagen expression. In contrast, knockdown of Ets-1 in glomeruli resulted in severe ECM deposition in diseased glomeruli. In conclusion, Ets-1 promotes degradation of ECM proteins and is critical for integral glomerular reorganization.

Original languageEnglish
Pages (from-to)298-305
Number of pages8
JournalKidney international
Volume70
Issue number2
DOIs
Publication statusPublished - 2006 Jul 7

Keywords

  • Gene therapy
  • Mesangial cells
  • TGF-β

ASJC Scopus subject areas

  • Nephrology

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