Angiotensin II inhibits insulin-induced egr-1 expression in mesangial cells.

The gene early growth response gene-1 (egr-1) encodes a zinc transcription factor involved in cell proliferation. Increased expression of egr-1 has been linked to heart and kidney disease. In mouse mesangial cells, insulin stimulated egr-1 expression more than angiotensin II, suggesting that insulin may play an important role in stimulating cell proliferation, leading to glomerulonephritis and diabetic nephropathy. Angiotensin II inhibited insulin-induced egr-1 expression but not c-fos expression, and the decrease in egr-1 expression was concurrent with a decrease in insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation. These results suggest that insulin-induced egr-1 expression in mouse mesangial cells is downstream of tyrosine phosphorylation of IRS-1 and activation of the MAP kinase pathway and that crosstalk between angiotensin II and insulin signaling pathways led to an inhibition of IRS-1 tyrosine phosphorylation and egr-1 expression.