Serum response elements mediate protein kinase C dependent transcriptional induction of early growth response gene-1 by arginine vasopressin in rat mesangial cells.

Abstract

Arginine vasopressin (AVP) regulates glomerular hemodynamics, alters extracellular matrix production, and induces proliferation of glomerular mesangial cells (MCs). Therefore, AVP may play a role in glomerular sclerosis and the progression of chronic renal failure. To investigate changes in early gene expression which may link intracellular biochemical events with changes in MC phenotype following AVP stimulation, we studied expression of the Early growth response gene-1 (Egr-1). Nuclear run off assays demonstrate that AVP induces Egr-1 at the transcriptional level. Transcriptional induction was, like induction of mitogenesis, dependent upon activation of protein kinase C (PK C). Promoter deletion analysis revealed that the region critical for Egr-1 inducibility by AVP contained several serum response element (SRE) consensus sequences. Sequential deletion of these SREs led to a drop in AVP-stimulated promoter activity. AVP was also able to stimulate transcription from a construct containing an Egr-1 SRE upstream of a heterologous promoter and this effect required activation of PK C. Electrophoretic mobility shift assays, using an Egr-1 SRE as probe, demonstrate up to four protein-SRE complexes of differing size that undergo modest quantitative changes following AVP stimulation. These data in MCs suggest that upstream SREs mediate transcriptional induction of Egr-1 by AVP in a PK C-dependent fashion and that changes in DNA-protein interaction involving the SREs may be in part responsible for this effect.