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[Egr-1 transcription factor regulates the growth of glomerular mesangium cells]
H D Rupprecht1, G Hofer, R B Sterzel
1Medizinische Klinik IV der Universität Enlangen-Nümberg.
Background:
The transcriptional regulator Early growth response gene-1 (Egr-1) is rapidly and transiently induced by various mitogens in cultured rat mesangial cells (MCs).
Method And Results:
Here we show Egr-1 induction in an in vivo model of mesangioproliferative glomerulonephritis (GN). A 14.9-fold increase in Egr-1 mRNA was observed 6 days after disease induction. A concomitant increase in Egr-1 protein was demonstrated by immunocytochemistry. Egr-1 was mainly localized to the nuclei of cells in mesangial localization. To test whether Egr-1 directly regulated MC proliferation, we preincubated cultured MCs with antisense oligonucleotides directed against Egr-1. The platelet-derived growth factor (PDGF)-induced increase in Egr-1 mRNA and protein levels was inhibited by 75% and 74%, respectively. At the same time Egr-1 antisense oligonucleotides dose-dependently inhibited MC-proliferation as determined by thymidine-uptake by up to 75%. Control oligonucleotides were without effects on Egr-1 mRNA, protein or MC growth.
Conclusion:
We conclude that Egr-1 induction is a necessary step in the mitogenic signaling cascade in glomerular MCs.