Chronic systemic treatment with epidermal growth factor induces smooth muscle cell hyperplasia and hypertrophy in the urinary tract of mature Goettingen minipigs

Abstract

Objective To determine the effect of systemic treatment 103 in the pigs treated with placebo and 55 (19-80) × 103 in those treated with EGF, and the median with epidermal growth factor (EGF) on the induction of growth in the urinary tract.(range) volume of the smooth muscle cells was 2.3 (2.2-2.4) × 103 and 4.0 (3.0-4.5) × 103 mm3 , Materials and methods Mature Goettingen minipigs were treated daily with vehicle (Tris-HCl; n=5) or EGF respectively. Conclusions There were two likely mechanisms contribu-(30 mg/kg) (n=6) for 4 weeks. The total number of smooth muscle cells was counted using an optical ting to smooth muscle cell hyperplasia, the division of fully differentiated smooth muscle cells and division of disector in a 20 mm thick cross-section of the ureter and the mean smooth muscle cell volume estimated.fibroblasts in the borderline between the submucosal layer and muscular coat, with ensuing differentiation Cell proliferation was detected by immunostaining for the marker Ki67.into smooth muscle cells. Treatment with EGF induces the growth of all wall layers in the urinary tract with Results The ureters of the animals treated with EGF were longer and thicker than those of the controls and the remarkable hyperplastic and hypertrophic changes of the smooth muscle cells in the muscular coat. median cross-sectional area of the ureter was 3.3-fold larger; the growth involved all wall layers. The median Keywords Epidermal growth factor, smooth muscle cells, hyperplasia, hypertrophy, pigs, urinary tract (range) number of smooth muscle cells in a 20 mm thick cross-section of the ureter was 11 (9-12) × suggested in vascular smooth muscle cells [6] and

Smooth Muscle Cell Hypertrophy and Hyperplasia in the Partially Obstructed Gut of the Rat: A Quantitative Evaluation

“…Data presented in this study are in line with those of the literature that demonstrated the relevant potentiality for cell proliferation of smooth muscle in various organs and species of mature animals, in relation to different experimental and/or pathological conditions [Cussen and Tymms, 1972;Gee and Kiviat, 1975;Gabella, 1990;Nguyen et al, 1996;VinterJensen et al, 1997]. Recent quantitative data on smooth muscle hyperplasia suggested that the degree of this phenomenon could be, in some conditions, even more pronounced than the coexisting cell hypertrophy [Nguyen et al, 1996;Vinter-Jensen et al, 1997]. In relation to this issue, data of the present study showed that the relationship among the four different morphological parameters that were investigated is different in upstream and downstream segments.…”

“…In these condtions, a 4-fold increase in the smooth muscle cell number was demonstrated. Further analysis confirmed the persistence of the proliferative capacity of the adult's smooth muscle in the ureter of other species as a consequence of an obstruction [Gee and Kiviat, 1975] and, recently, as a conSmooth Muscle Cell Hypertrophy and Hyperplasia in the Partially Obstructed Gut of the Rat: A Quantitative Evaluation sequence of systemic treatment with epidermal growth factor [Vinter-Jensen et al, 1997]. In addition, the capacity for cell proliferation in the smooth muscle has been assessed in other organs under particular experimental and/or pathological conditions, such as vessels of hypertensive rats [Owens and Reidy, 1985;Owens, 1985Owens, , 1989, myometrium during treatment with estrogen [Martin et al, 1973], airway smooth muscle underlying bronchial asthma [Page and Coyle, 1989;Ebina et al, 1993], smooth muscle at various levels of the gastroenteric system, after resection [Jurukova and Atanassova, 1974;Nguyen et al, 1996] and after partial obstruction [Gabella, 1975[Gabella, , 1979[Gabella, , 1990Brossa et al, 1992a, Canavese et al, 1992.…”

Epidermal growth factor in clinical practice – a review of its biological actions, clinical indications and safety implications

“…As shown in Table 3, numerous preclinical studies based on long-term systemic administration of EGF at supra-physiological concentrations concluded that EGF induces epithelial hyperplasia that appeared to depend on the dose and length of the exposure time (references (79)(80)(81)(82)(83)(84)(85)(86)(87)(88)). The excessive epithelial growth was reversible upon treatment withdrawal.…”

Alterações morfométricas da musculatura dos músculos longitudinal e circular de ratos submetidos à criação de piloros no intestino delgado

“…A possibilidade da célula muscular sofrer duplicação foi uma conquista recente da pesquisa 13 . A célula muscular vai à mitose simples ou, através da diferenciação dos fibroblastos situados na linha de transição entre a submucosa e a camada muscular, em células musculares levando ao aumento do número delas, fato que é auxiliado pelo estímulo do hormônio de crescimento 15 .…”