Prevention of renal vascular and glomerular fibrosis by epidermal growth factor receptor inhibition

SPECIFIC AIMSHypertension is often associated with the development of renal vascular and glomerular fibrosis, a pathological process characterized by abnormal accumulation of extracellular matrix (mainly collagens) within the renal vasculature. The purpose of the present study was to investigate whether epidermal growth factor receptor (EGFR) activation participates in the development of renal fibrosis and to test whether blockade of EGFR activation would have therapeutic effects.PRINCIPAL FINDINGS1. EGFR activation in renal cortex during NO deficiencyThese experiments were performed in a model of hypertension-induced chronic renal failure, the NO deficiency model. NO synthesis was inhibited by administrating a NO synthase inhibitor, L-NAME. In this model, 4–6 wk of L-NAME treatment are enough to develop renal vascular and glomerular fibrosis in rats.Systolic blood pressure rose after 4 wk of L-NAME treatment (P<0.01, Fig. 1⤻ , upper panel). To test the status of activation of the EGFR, Western blot was p...