Mesangial cell expression of proto-oncogene Ets-1 during progression of mesangioproliferative glomerulonephritis

Kidney Int. 2004 Aug;66(2):622-32. doi: 10.1111/j.1523-1755.2004.00782.x.


Background: Ets-1 is a transactivator of matrix-associated genes and key factor in neoangiogenesis. The expression of Ets-1 mRNA and protein was analyzed in healthy rat kidney and in a model for mesangioproliferative disease without and with inhibition of platelet-derived growth factor-B (PDGF-B) activity.

Methods: Immunohistochemistry was performed using a specific noncrossreacting anti-Ets-1 antibody and included a counterstain with alpha-smooth muscle actin (alpha-SMA). Nuclear proteins from isolated glomeruli were analyzed by Western blotting. Changes in Ets-1 mRNA levels were detected by in situ hybridization and Northern blotting. PDGF-B antagonism was performed in nephritic rats by specific aptamers.

Results: The distribution of Ets-1-positive cells in healthy rats was heterogenous with exclusively nuclear staining of glomerular, tubular, and vascular cells. Profound changes were detected in the anti-Thy 1.1 glomerulonephritis. Nuclear Ets-1 staining was intense in mesangial cells, whereas podocyte and endothelial cell staining was unchanged. The strongest signal was seen on days 2 to 7. By Western blotting of glomerular proteins a single 52 kD band was detected in healthy rats, which was increased 4.5-fold after disease induction. At the same time a 54 kD band appeared that most likely represents phosphorylated Ets-1. Ets-1 transcripts were detected in mesangial cells that include exon IV but lack exon VII. A concordant 6.4-fold up-regulation of mRNA was detected in glomeruli. Specific PDGF-B antagonism by aptamer treatment from days 3 to 7 after disease induction led to reduced Ets-1 expression on day 7, correlating with decreased mesangial cell numbers.

Conclusion: A temporal increase of mesangial cell Ets-1 expression correlates with mesangial cell activation in mesangioproliferative glomerulonephritis. PDGF-B may partially contribute to the increased expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Animals
  • Blotting, Northern
  • Cells, Cultured
  • Disease Models, Animal
  • Disease Progression
  • Gene Expression / physiology
  • Glomerular Mesangium / cytology
  • Glomerular Mesangium / physiology*
  • Glomerulonephritis, Membranoproliferative / metabolism
  • Glomerulonephritis, Membranoproliferative / physiopathology*
  • In Situ Hybridization
  • Isoantibodies
  • Male
  • Proto-Oncogene Protein c-ets-1
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-ets
  • Proto-Oncogene Proteins c-sis / antagonists & inhibitors
  • RNA, Messenger / analysis
  • Rats
  • Rats, Wistar
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism


  • Ets1 protein, rat
  • Isoantibodies
  • Proto-Oncogene Protein c-ets-1
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • Proto-Oncogene Proteins c-sis
  • RNA, Messenger
  • Transcription Factors
  • anti-Thy antibody