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 with 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 disector in a 20 mu m thick cross-section of the meter and the mean smooth muscle cell volume estimated. Cell proliferation was detected by immunostaining for the marker Ki67. Results The meters of the animals treated 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 growth involved all wall layers. The median (range) number of smooth muscle 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 those treated with EGF, and the median (range) volume of the smooth muscle cells was 2.3 (2.2-2.4) x 10(3) and 4.0 (3.0-4.5) x 10(3) mm(3), respectively. Conclusions There were two likely mechanisms contributing to smooth muscle cell hyperplasia, the division of fully differentiated smooth muscle cells and division of fibroblasts in the borderline between the submucosal layer and muscular coat, with ensuing differentiation 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.