RGD Reference Report - Transcription factor Egr-1 regulates glomerular mesangial cell proliferation. - Rat Genome Database

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Transcription factor Egr-1 regulates glomerular mesangial cell proliferation.

Authors: Hofer, G  Grimmer, C  Sukhatme, VP  Sterzel, RB  Rupprecht, HD 
Citation: Hofer G, etal., J Biol Chem. 1996 Nov 8;271(45):28306-10.
RGD ID: 8553929
Pubmed: PMID:8910451   (View Abstract at PubMed)

Increase of glomerular mesangial cells (MCs) is a prominent histopathological finding in many types of glomerulonephritis. We have shown previously that expression of the zinc-finger transcription factor, early growth response gene-1 (egr-1), is closely correlated with the proliferation of cultured MCs. To elucidate whether Egr-1 is required for MC proliferation, we inhibited serum-induced Egr-1 expression by phosphothioate-modified antisense oligonucleotides (ODNs). Uptake of antisense ODNs into MCs was demonstrated, and five different egr-1 antisense ODNs were tested for their impact on serum-induced egr-1 mRNA and protein levels and on MC growth. The most potent egr-1 antisense ODN inhibited serum-induced egr-1 mRNA by 68%, protein induction by 58%, and MC replication as measured by [3H]thymidine uptake and cell counts by 78 and 46%, respectively. The effects of antisense ODNs on MC growth correlated closely with their ability to inhibit Egr-1 protein. ODNs acted in a dose-dependent manner, the minimal effective concentration being 1 microM. Control ODNs had no significant effects. In addition, antisense ODNs against egr-1 potently inhibited endothelin-1-induced Egr-1 expression and MC growth. Heparin, a known inhibitor of MC growth, suppressed serum-induced [3H]thymidine uptake by 39% and egr-1 mRNA expression by 44%. We conclude that Egr-1 is an essential part of the mitogenic signal transduction cascade in cultured MCs.

Gene Ontology Annotations    

Biological Process

Cellular Component
cytoplasm  (IDA)
nucleus  (IDA)

Objects Annotated

Genes (Rattus norvegicus)
Egr1  (early growth response 1)

Additional Information