INCREASED EPIDERMAL GROWTH-FACTOR IN EXPERIMENTAL DIABETES-RELATED KIDNEY GROWTH IN RATS

Renal enlargement is a characteristic feature of human and experimenta l diabetes mellitus that may be predictive of subsequent nephropathy. In the streptozotocin diabetic rat kidney growth rapidly follows the i nduction of experimental diabetes but the mechanisms responsible for t his growth are poorly understood. Epidermal growth factor (EGF) is a p otent mitogen for renal tubular cells. Thirty one male Sprague-Dawley rats aged 13 weeks were randomised to receive either streptozotocin (d iabetic, n = 20) or buffer (control, n = 11). Animals were studied on days 1, 3, 5 and 7 following streptozotocin. Diabetes was associated w ith a 3-fold increase in urinary EGF excretion (223 +/- 15 vs 59 +/- 5 ng/day, mean +/- SEM, diabetic vs control, p < 0.0001) and 3-6 fold i ncrease in renal EGF mRNA relative to controls (p < 0.001). A transien t rise in kidney EGF protein was noted on day 1. There was no differen ce between diabetic and control animals with regard to intrarenal site s of EGF expression or in plasma EGF These data suggest that the incre ased urinary EGF excretion in diabetic animals is the result of enhanc ed local production and that EGF is not stored for a prolonged period within renal tubular cells but is released following its synthesis. In the context of the known intrarenal actions of EGF this growth fact o r may play a role in the pathogenesis of diabetes related kidney growt h.