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.
Solow
B T
BT
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, D101 Richards Building, 37th and Hamilton Walk, Philadelphia, Pennsylvania 19104, USA.
Derrien
A
A
Smith
J A
JA
Jarett
L
L
Harada
S
S
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins / Q000235:genetics*; D051766:Early Growth Response Protein 1; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos / Q000187:drug effects; D005920:Glomerular Mesangium / Q000187:drug effects* / Q000378:metabolism*; D017874:Immediate-Early Proteins; D007328:Insulin / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins; D007674:Kidney Diseases / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics
D016895:Culture Media, Serum-Free; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486109:Egr1 protein, mouse; D017874:Immediate-Early Proteins; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D010750:Phosphoproteins; D014157:Transcription Factors; D000804:Angiotensin II; D011972:Receptor, Insulin