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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Delella, Flavia K. [1, 2] ; Lacorte, Livia M. [2] ; Almeida, Fernanda Losi A. [3] ; Dal Pai, Maeli [2] ; Felisbino, Sergio L. [2]
Total Authors: 5
Affiliation:
[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
Total Affiliations: 3
Document type: Journal article
Source: Life Sciences; v. 91, n. 25-26, p. 1281-1287, DEC 17 2012.
Web of Science Citations: 5
Abstract

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)