[Egr-1 transcription factor regulates the growth of glomerular mesangium cells].
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).


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.


CONCLUSIONS
We conclude that Egr-1 induction is a necessary step in the mitogenic signaling cascade in glomerular MCs.
Rupprecht
H D
HD
Medizinische Klinik IV der Universität Enlangen-Nümberg.
Hofer
G
G
Sterzel
R B
RB
Schöcklmann
H O
HO
D000818:Animals; D002455:Cell Division / Q000235:genetics; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics*; D051766:Early Growth Response Protein 1; D015870:Gene Expression / Q000502:physiology; D005920:Glomerular Mesangium / Q000473:pathology*; D015432:Glomerulonephritis, Membranoproliferative / Q000235:genetics* / Q000473:pathology; D017874:Immediate-Early Proteins; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D012333:RNA, Messenger; D014157:Transcription Factors
Der Transkriptionsfaktor Egr-1 reguliert das Wachstum glomerulärer Mesangiumzellen.