CHRONIC SYSTEMIC TREATMENT WITH EPIDERMAL GROWTH-FACTOR INDUCES SMOOTH-MUSCLE CELL HYPERPLASIA AND HYPERTROPHY IN THE URINARY-TRACT OF MATURE GOETTINGEN MINIPIGS

Objective To determine the effect of systemic treatment with epidermal growth factor (EGF) on the induction of growth in the urinary tract. Materials and methods Mature Goettingen minipigs were treated daily wi th vehicle (Tris-HCl; n=5) or EGF (30 mu g/kg) (n=6) for 4 weeks. The total number of smooth muscle cells was counted using an optical disec tor in a 20 mu m thick cross-section of the meter and the mean smooth muscle cell volume estimated. Cell proliferation was detected by immun ostaining for the marker Ki67. Results The meters of the animals treat ed with EGF were longer and thicker than those of the controls and the median cross-sectional area of the ureter was 3.3-fold larger; the gr owth involved all wall layers. The median (range) number of smooth mus cle cells in a 20 mu m thick cross-section of the meter was 11 (9-12) x 10(3) in the pigs treated with placebo and 55 (19-80) x 10(3) in tho se treated with EGF, and the median (range) volume of the smooth muscl e cells was 2.3 (2.2-2.4) x 10(3) and 4.0 (3.0-4.5) x 10(3) mm(3), res pectively. Conclusions There were two likely mechanisms contributing t o smooth muscle cell hyperplasia, the division of fully differentiated smooth muscle cells and division of fibroblasts in the borderline bet ween the submucosal layer and muscular coat, with ensuing differentiat ion into smooth muscle cells. Treatment with EGF induces the growth of all wall layers in the urinary tract with remarkable hyperplastic and hypertrophic changes of the smooth muscle cells in the muscular coat.