Expression of the transcriptional regulator Egr-1 in experimental glomerulonephritis: requirement for mesangial cell proliferation

Kidney International
H D RupprechtH O Schoecklmann

Abstract

The early growth response gene-1 (Egr-1), a zinc finger transcriptional regulator, was induced in a rat model of mesangioproliferative glomerulonephritis (GN). Northern blot analysis revealed a maximal 14.9-fold increase in glomerular Egr-1 mRNA at day 6 of GN. By immunohistochemistry Egr-1 protein expression was demonstrated to be mainly confined to glomerular mesangial cells (MC). To test whether Egr-1 directly regulates MC proliferation, cultured MCs were stimulated with platelet-derived growth factor (PDGF) after preincubation with different Egr-1 antisense oligonucleotides (ASOs). PDGF-induced rise in 3H-thymidine uptake by 83% and almost completely abrogated increase in MC number. We conclude that Egr-1 induction is of critical importance for PDGF-induced mitogenic signaling in MCs, and inhibition of Egr-1 in vivo may offer an approach to oppose glomerular MC proliferation in glomerular inflammatory disease.

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Related Concepts

Zinc Fingers
Membranoproliferative Glomerulonephritis, Type II
Immediate-Early Proteins
Thymidine
Egr1
Gene Expression
Cell Division Phases
Egr1 protein, rat
Poly(A) Tail
DNA Helix Destabilizing Proteins

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