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    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to heparin involved_inIDA 8553929PMID:8910451UniProt 
positive regulation of glomerular metanephric mesangial cell proliferation involved_inIMP 8553929PMID:8910451UniProt 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cytoplasm located_inIDA 8553929PMID:8910451UniProt 
nucleus located_inIDA 8553929PMID:8910451UniProt 

Objects Annotated

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

Additional Information