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.
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.
Authors: X M Cao; R A Koski; A Gashler; M McKiernan; C F Morris; R Gaffney; R V Hay; V P Sukhatme Journal: Mol Cell Biol Date: 1990-05 Impact factor: 4.272
Authors: T B Kinane; J D Finder; A Kawashima; D Brown; M Abbate; C Shang; W J Fredericks; F J Rauscher; V P Sukhatme; L Ercolani Journal: J Biol Chem Date: 1994-11-04 Impact factor: 5.157
Authors: V P Sukhatme; X M Cao; L C Chang; C H Tsai-Morris; D Stamenkovich; P C Ferreira; D R Cohen; S A Edwards; T B Shows; T Curran Journal: Cell Date: 1988-04-08 Impact factor: 41.582