Bruni-Cardoso Alexandre, Vilamaior Patrícia S L, Taboga Sebastião R, Carvalho Hernandes F
Department of Cell Biology, State University of Campinas (UNICAMP), Campinas, SP, Brazil.
Histochem Cell Biol. 2008 Jun;129(6):805-15. doi: 10.1007/s00418-008-0407-x. Epub 2008 Mar 5.
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.
前列腺形态发生的初始事件包括细胞增殖、上皮管道形成以及向基质的生长。我们推测基质重排发生在上皮生长和分支的部位，并且这种重排涉及明胶酶基质金属蛋白酶（MMP）-2和MMP-9的作用。因此，本研究的目的是描述大鼠腹侧前列腺出生后第一周上皮生长的结构特征，并通过组织学、超微结构和免疫细胞化学分析，以及凝胶酶谱分析、原位酶谱分析和蛋白质印迹法，研究此期间MMP-2和MMP-9的表达、定位及活性。在出生后的第一周内观察到前列腺结构的复杂性增加。同时，基质变得更加有序，一些细胞分化为平滑肌细胞。网状纤维以篮状排列出现在生长尖端和上皮芽周围，伴层粘连蛋白染色变浅。检测到MMP-2和MMP-9的活性。在第一周内MMP-2/MMP-9表达下降。发育中的上皮索显示出强烈且弥漫的明胶溶解活性。这种活性与免疫细胞化学测定的MMP-2分布一致。另一方面，MMP-9相当集中在上皮尖端。这些结果表明，上皮内以及上皮-基质界面的明胶溶解活性（由MMP-2和MMP-9共同作用）至少部分负责组织重塑，从而允许上皮生长并向周围基质中突出。
