SERUM RESPONSE ELEMENTS MEDIATE PROTEIN-KINASE-C DEPENDENT TRANSCRIPTIONAL INDUCTION OF EARLY GROWTH-RESPONSE GENE-1 BY ARGININE-VASOPRESSIN IN RAT MESANGIAL CELLS

Arginine vasopressin (AVP) regulates glomerular hemodynamics, alters e xtracellular matrix production, and induces proliferation of glomerula r 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 biochem ical events with changes in MC phenotype following AVP stimulation, we studied expression of the Early growth response gene-1 (Egr-1). Nucle ar run off assays demonstrate that AVP induces Egr-1 at the transcript ional level. Transcriptional induction was, like induction of milogene sis, dependent upon activation of protein kinase C (PK C). Promoter de letion analysis revealed that the region critical for Egr-1 inducibili ty by AVP contained several serum response element (SRE) consensus seq uences. Sequential deletion of these SREs led to a drop in AVP-stimula ted promoter activity. AVP was also able to stimulate transcription fr om a construct containing an Egr-1 SRE upstream of a heterologous prom oter and this effect required activation of PK C. Electrophoretic mobi lity shift assays, using an Egr-1 SRE as probe, demonstrate up to four protein-SRE complexes of differing size that undergo modest quantitat ive changes following AVP stimulation. These data in MCs suggest that upstream SREs mediate transcriptional induction of Egr-1 by AVP in a P K C-dependent fashion and that changes in DNA-protein interaction invo lving the SREs may be in part responsible (c)or this effect. (C) 1994 Wiley-Liss, Inc.