Fibrosis-related gene expression in the prostate is modulated by doxazosin treatment

Autor(es)

Delella, Flavia K. ^{[1, 2]} ; Lacorte, Livia M. ^[2] ; Almeida, Fernanda Losi A. ^[3] ; Dal Pai, Maeli ^[2] ; Felisbino, Sergio L. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Campinas UNICAMP, Inst Biol, Dept Struct & Funct Biol, Campinas, SP - Brazil

^[2] Univ Estadual Paulista UNESP, Inst Biosci, Dept Morfol, BR-18618970 Botucatu, SP - Brazil

^[3] State Univ Maringa UEM, Dept Morphol Sci, Maringa, Parana - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Life Sciences; v. 91, n. 25-26, p. 1281-1287, DEC 17 2012.
• Citações Web of Science: 5

Resumo

Aims: To gain new insights into the molecular mechanisms of action of doxazosin, we investigated the prostatic stroma ultrastructure and the expression of genes involved with fibrosis, such as collagen type I and III (COL1A1 and COL3A1, respectively) and TGF-beta 1, in the rat ventral prostate. Main methods: Adult Wistar rats were treated with doxazosin (25 mg/kg/day), and the ventral prostates were excised at 7 and 30 days after treatment. Untreated rats were controls. Ventral prostates were subjected to ultrastructural, immunohistochemical, biochemical and molecular analyses. Key findings: Doxazosin-treated prostates showed thickened bundles of collagen fibrils, activated fibroblasts, enlarged neurotransmitter vesicles and increased tissue immunostaining for collagen type I and type III when compared to untreated prostates. After 7 and 30 days of doxazosin treatment mRNA expression of COL1A1 and COL3A1 was significantly increased and reduced, respectively, compared to the control group. TGF-beta 1 mRNA and protein levels were increased after 7 days of doxazosin treatment, whereas only mRNA levels remained increased after 30 days of treatment. Significance: Our data suggest that relaxation of smooth muscle cells by alpha-blockers interferes with the mechanical dynamics of the prostatic stroma extracellular matrix components, generating a pro-fibrotic effect probably via the TGF-beta 1 signaling pathway. Long term treatment with doxazosin may also lead to a reduced turnover of extracellular matrix components. Our results add to a better understanding of the molecular mechanisms behind the effects of alpha-blockade on prostatic histoarchitecture and the response to treatment for benign prostatic hyperplasia. (C) 2012 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 06/60114-6 - Efeito da finasterida e da doxazosina sobre os diferentes lobos da prostata de rato: analise ultraestrutural e da expressao dos colagenos tipo i e iii e do tgf-beta 1.
• Beneficiário: Flávia Karina Delella
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 06/60115-2 - Efeito do diabete e da reposicao com insulina sobre o processo de maturacao da prostata ventral do rato wistar: alteracoes morfologicas e na atividade de metaloproteinases de matriz mmp-2 e -9.
• Beneficiário: Sérgio Luis Felisbino
• Modalidade de apoio: Auxílio à Pesquisa - Regular