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Heparanase-1 activity and the early postnatal prostate development.

Guilherme Oliveira Barbosa1, Alexandre Bruni-Cardoso2, Maria Aparecida da Silva Pinhal3

  • 1Departamento de Biologia Estrutural e Funcional, Universidade Estadual de Campinas, Instituto de Biologia, Campinas, São Paulo, Brazil.

Developmental Dynamics : an Official Publication of the American Association of Anatomists
|January 18, 2019
PubMed
Summary

Heparanase-1 (HPSE) is crucial for ventral prostate (VP) development. This study shows HPSE regulates early VP epithelial growth by influencing heparan sulfate (HS) signaling and growth factor availability.

Keywords:
Developmentepithelial morphogenesisheparan sulfateheparanaseprostate

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Area of Science:

  • Developmental biology
  • Cell signaling
  • Biochemistry

Background:

  • Ventral prostate (VP) morphogenesis is a complex process influenced by paracrine signaling.
  • Heparan sulfate (HS) plays a key role in modulating these signals.
  • Heparanase-1 (HPSE), the enzyme that cleaves HS, is critical for releasing bioactive HS fragments and growth factors, but its role in VP development is largely unknown.

Purpose of the Study:

  • To investigate the expression and function of HPSE during rat ventral prostate morphogenesis.
  • To determine the impact of HS modulation and HPSE activity on VP epithelial growth in early postnatal development.

Main Methods:

  • Analysis of heparan sulfate proteoglycan (HSPG) and HPSE expression in rat VP.
  • Ex vivo culture of rat VP treated with heparin or Hpse siRNA.
  • Size-exclusion chromatography to assess HS chain length.
  • Western blotting to evaluate ERK1/2 phosphorylation and expression of MMP2 and MMP9.

Main Results:

  • HPSE was primarily expressed in the VP epithelium.
  • Heparin treatment or Hpse knockdown in ex vivo cultures delayed VP epithelial growth.
  • Hpse silencing altered HS chain length, modulated MMP2 and MMP9 expression, and reduced ERK1/2 phosphorylation.

Conclusions:

  • HPSE is essential for early postnatal VP epithelial growth.
  • HPSE activity influences HS turnover, growth factor bioavailability, and signaling pathways like ERK1/2.
  • These findings highlight HPSE as a key regulator of VP development.