Upregulation of epidermal growth factor and its receptor in the kidneys of rats with streptozotocin-induced diabetes

Abstract

We have studied the acute changes (up to 30 days) in the expression of epidermal growth factor (EGF) and its receptor (EGFr) in the kidneys of adult male Wistar rats made diabetic by a single intravenous injection of streptozotocin (55 mg/kg) using a combination of immunocytochemical staining and in situ hybridization histochemistry. In the absence of insulin treatment, diabetic rats displayed renal growth (hypertrophy and hyperplasia). It was accompanied by an increase in immunostainable EGF within the thick ascending limb (TAL) of the loops of Henle which was apparent within 24 h of the onset of diabetes, reached a peak by day 7 and persisted to the end of the experimental period (day 30). In situ hybridization histochemistry revealed that these changes were preceded by a rapid rise in EGF mRNA in the cells of the TAL, which was highest after 1 day but declined to control levels by day 7. Increased immunostainable EGFr was evident in both the proximal and TAL and in the cortical collecting ducts from day 1. Staining of the proximal tubules declined rapidly after day 1 but that of the TAL and collecting ducts persisted until day 7 and declined thereafter. These results are discussed in light of the role of EGF in the hypertrophy and repair of the diabetic kidney.