Involvement of matrix metalloproteinases in the rodent ventral prostate development and regression

Author(s)

Alexandre Bruni Cardoso

• Document type: Doctoral Thesis
• Press: Campinas, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia
• Defense date: 2010-02-24

Examining board members

Hernandes Faustino de Carvalho; Ruy Gastaldoni Jaeger; Maria Christina Werneck de Avellar; Sérgio Luis Felisbino; Willian Fernando Zambuzzi

• Advisor: Hernandes Faustino de Carvalho

Abstract

The prostate is an important gland of the reproductive tract of mammals, which is a target of several benign and malign diseases affecting the elder. Both postnatal prostate development and prostate regression after androgenic ablation are characterized by intense modification in cell behavior and remodeling of extracellular matrix (ECM). MMPs constitute a family of endopeptidases which are able to cleave preferentially ECM components. Thus, it seems reasonable that these enzymes play a crucial role in tissue remodeling that happens during the ventral prostate (VP) morphogenesis and in the prostate regression after castration. In this study, we aimed to define the involvment of MMP-2 in the postnatal prostate development of rodent and the involvement of MMP-2, -7 and -9 rat ventral prostate regression after castration. For this aim, we have used molecular, biochemical and morphological approaches. siRNA specific for MMP-2 compromised the rat VP growth, branching, lumen formation and epithelial cell proliferation, besides leading an accumulation of collagen fibers in the stroma. MMP-2-/- VP showed a reduced relative weight and epithelial volume, besides displaying a decreased epithelial proliferation and branching and a stabilization of collagen matrix at the end of the first postnatal week. In the prostate regression after castration, we found multiple waves of cell death and a direct association between activity and expression of MMP-2, -7 and -9 and an apoptotic peak that occurs at the 11th Day after castration. In conclusion, the results presented here showed that both postnatal prostate development and prostate regression after castration are dependent on the expression and activity of MMPs. (AU)

• FAPESP's process: 05/04631-9 - Regulating the function of matrix metalloproteinases and their inhibitors in hormonal modulation during in vitro prostate development
• Grantee: Alexandre Bruni Cardoso
• Support Opportunities: Scholarships in Brazil - Doctorate