Abstract
We have hypothesized that epithelial growth, branching, and canalization
in the rodent ventral prostate (VP) would require matrix remodeling, and
hence matrix metalloproteinase (MMP) activity. Therefore, the aim of
this study was to evaluate the impact of blocking MMP-2, using whole
organ culture. siRNA was employed to inhibit MMP-2 expression, and this
was compared to GM6001's (a broad-spectrum MMP inhibitor) inhibition of
general MMPs. These blocks impaired VP morphogenesis. MMP-2 silencing
reduced organ size, epithelial area, and the number of tips, as well as
caused a dilation of the distal parts of the epithelium. Histology, 3-D
reconstruction, biochemistry, and second harmonic generation (SHG)
revealed that MMP-2 silencing affected VP architecture by interfering in
epithelial cell proliferation, lumen formation, and cellular
organization of both epithelium and stroma, besides intense accumulation
of collagen fibers. These data suggest that MMP-2 plays important roles
in prostate growth, being directly involved with epithelial
morphogenesis. Developmental Dynamics 239:737-746, 2010. (C) 2010
Wiley-Liss, Inc.
Users
Please
log in to take part in the discussion (add own reviews or comments).