Localized matrix metalloproteinase (MMP)-2 and MMP-9 activity in the rat ventral prostate during the first week of postnatal development

Abstract

The initial events in prostatic morphogenesis involve cell proliferation, epithelial canalization and outgrowth toward the stroma. We have hypothesized that stromal rearrangement takes place at the sites of epithelial growth and branching and that this rearrangement involves the action of gelatinases matrix metalloproteinase (MMP)-2 and MMP-9. Thus, the purpose of the present study was to characterize structural aspects of epithelial growth during the first week of postnatal development of the rat ventral prostate and to investigate the expression, localization and activity of MMP-2 and MMP-9 during this period by histological, ultrastructural and immunocytochemical analysis, in addition to gel zymography, in situ zymography and Western blotting. An increasing complexity of prostatic architecture was observed within the first postnatal week. Concurrently, the stroma became more organized and some cells differentiated into smooth muscle cells. Reticulin fibers appeared in a basket-like arrangement around both growing tips and epithelial sprouts, associated with a fainter staining for laminin. MMP-2 and MMP-9 activities were detected. MMP-2/MMP-9 expression decreased during the first week. Developing epithelial cords showed strong and difuse gelatinolytic activity. This activity coincided with the distribution of MMP-2 as determined by immunocytochemistry. On the other hand, MMP-9 was rather concentrated at the epithelial tips. These results suggest that gelatinolytic activity (with contribution of both MMP-2 and MMP-9) in the epithelium and at the epithelium-stroma interface are at least in part responsible for the tissue remodeling that allows epithelial growth and its projection into the surrounding stroma.

MMP‐2 contributes to the development of the mouse ventral prostate by impacting epithelial growth and morphogenesis

“…Using immunohistochemistry, MMP-2 was found in the mouse VP on day 6, in both stroma and epithelium, being more concentrated in the epithelial distal regions (Fig. 1A), suggesting a role for this enzyme during epithelial branching and elongation, findings that are in agreement with our earlier in vitro and ex vivo studies in the rat (Bruni-Cardoso et al, 2008. Tissue organization was determined by stereology.…”

“…Using an in vitro/ex vivo organogenesis model, we previously reported that the activities of MMP-2 and -9 are higher and localized in the distal ductal region and at the epithelial/ stromal interface of rat VP during the first postnatal week (Bruni-Cardoso et al, 2008). Subsequently, we showed that MMP-2 modulates the morphogenesis of the rat ventral prostate in vitro by influencing the epithelial cell proliferation rate, branching, and the canalization of the epithelium, and the remodeling of collagen fibers (Bruni-Cardoso et al, 2010).…”

“…VP paraffin sections submitted to Gömöri's silver impregnation staining were used for the identification of reticulin fibers, as previously described (Bruni-Cardoso et al, 2008). Briefly, the procedure involves sequential treatment with 1% potassium permanganate, 3% oxalic acid, and 1% iron alumen followed by incubation with 10% ammoniacal silver.…”

“…In humans, prostate development takes place during the second and third trimester of gestation; whereas in rodents, the prostate gland displays significant growth and morphogenetic changes during the first postnatal week. In this period, the epithelial cells proliferate and differentiate, together with epithelial growth, branching, and canalization (Sugimura et al, 1986a;Donjacour and Cunha, 1988;Hayward et al, 1996;Bruni-Cardoso and Carvalho, 2007;Bruni-Cardoso et al, 2008). Epithelial growth involves colonization of spaces previously occupied by the mesenchyme/ stroma .…”

Modulação androgênica e estrogênica na próstata: uma abordagem em modelos experimentais de roedores com enfoque na biologia estrutural

“…Estes, por sua vez, irão estimular atividades específicas nas células prostáticas, como a proliferação das células epiteliais (KGF) e estromais (FGF). Durante o desenvolvimento embrionário, por exemplo, as células mesenquimais do complexo prostático em desenvolvimento são as primeiras a expressar AR e, então, sob o estímulo androgênico, liberam fatores como o FGF-10 que agem sobre as células epiteliais induzindo a formação dos ductos prostáticos e seu padrão de ramificação característico (14,15,17,18). Por sua vez, a ação direta dos andrógenos se aplica principalmente para a regulação da atividade secretora das células epiteliais (19).…”