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- Title
Heparanase‐1 activity and the early postnatal prostate development.
- Authors
Barbosa, Guilherme Oliveira; Bruni‐Cardoso, Alexandre; da Silva Pinhal, Maria Aparecida; Augusto, Taize Machado; Carvalho, Hernandes F.
- Abstract
Ventral prostate (VP) morphogenesis starts during embryonic development and continues for the first three postnatal weeks. Heparan sulfate (HS) affects paracrine signaling. Heparanase‐1 (HPSE) is the only enzyme capable of cleaving HS. HPSE releases the HS bioactive fragment and mobilizes growth factors. Little is known, however, about HS turnover and HPSE function during VP morphogenesis. In this study, we measured HSPG expression and analyzed the expression and distribution of HPSE in the rat VP. HPSE was predominantly expressed by the VP epithelium. The VP was treated with heparin in ex vivo cultures to interfere with HS and resulted in delayed epithelial growth. Hpse knockdown using siRNA delayed epithelial growth in the first postnatal week ex vivo, which was similar to treating with the lower concentration of heparin. Hpse silencing was related to changes in HS chain length (as determined by size‐exclusion chromatography, up‐regulation of Mmp9, and down‐regulation of Mmp2 expression). It also down‐modulated ERK1/2 phosphorylation, suggesting a reduction in signaling, likely due to decreased HS cleavage and growth factor bioavailability. Our results showed that HPSE played a role in early epithelial growth during the first week of VP postnatal development. Developmental Dynamics 248:211‐220, 2019. © 2019 Wiley Periodicals, Inc. Key Findings: Heparan sulfate proteoglycans are differentially expressed during early postnatal VP development.Either HPSE inhibition or knocking‐down compromises epithelial growth during postnatal VP development.Hpse expression correlates positively with Mmp2 and negatively with Mmp9.HPSE silencing negatively regulates ERK1/2 signaling.
- Publication
Developmental Dynamics, 2019, Vol 248, Issue 3, p211
- ISSN
1058-8388
- Publication type
Article
- DOI
10.1002/dvdy.12