Specific inhibition of Egr-1 prevents mesangial cell hypercellularity in experimental nephritis

Kidney Int. 2003 Apr;63(4):1302-12. doi: 10.1046/j.1523-1755.2003.00865.x.


Background: Mesangial cell proliferation is a frequent finding in glomerulonephritis. In cultured mesangial cells, we demonstrated that inhibition of the zinc finger transcription factor, early growth response gene-1 (Egr-1), by specific antisense oligonucleotides (AS ODN) blocks mesangial cell proliferation. Therefore, we here investigated the effect of Egr-1 inhibition on the course of an experimental mesangioproliferative glomerulonephritis in vivo.

Methods: On day 3 after induction of anti-Thy-1.1 nephritis, specific glomerular oligonucleotide transfer was achieved by injection of an oligonucleotide/hemagglutinating virus of Japan/liposome mixture into the left renal artery. The right kidney was left untreated.

Results: Induction of nephritis led to a sixfold induction of Egr-1 protein on day 6 of disease. This increase in Egr-1 expression was reduced by 48% in the left kidney by transfer of specific AS ODN. In parallel, the increases in glomerular cellularity, number of mitoses, and glomerular tuft area observed in day 6 nephritic animals were inhibited in the left kidney by 60%, 53%, and 50%, respectively. Changes in the right kidney were not significantly influenced. Likewise, control oligonucleotides showed no effect. Finally, the expression of platelet-derived growth factor-B (PDGF-B), a known target gene of Egr-1, was repressed by transfer of specific AS ODN against Egr-1.

Conclusion: We conclude that the transcription factor Egr-1 plays a critical role for mesangial cell proliferation in vivo. Interfering with the induction of Egr-1 or with its target genes could give rise to novel therapeutic principles in mesangioproliferative glomerulonephritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division
  • DNA-Binding Proteins / genetics*
  • Early Growth Response Protein 1
  • Gene Transfer Techniques*
  • Glomerular Mesangium / pathology*
  • Glomerulonephritis, Membranoproliferative / pathology*
  • Glomerulonephritis, Membranoproliferative / prevention & control*
  • Glomerulonephritis, Membranoproliferative / therapy
  • Immediate-Early Proteins*
  • Isoantibodies
  • Liposomes
  • Male
  • Mitosis
  • Oligonucleotides, Antisense / pharmacology
  • Proto-Oncogene Proteins c-sis / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Sendai virus / genetics
  • Transcription Factors / genetics*


  • DNA-Binding Proteins
  • Early Growth Response Protein 1
  • Egr1 protein, rat
  • Immediate-Early Proteins
  • Isoantibodies
  • Liposomes
  • Oligonucleotides, Antisense
  • Proto-Oncogene Proteins c-sis
  • Transcription Factors
  • anti-Thy antibody