Prostatic Inflammation Induces Fibrosis in a Mouse Model of Chronic Bacterial Infection

Inflammation of the prostate is strongly correlated with development of lower urinary tract symptoms and several studies have implicated prostatic fibrosis in the pathogenesis of bladder outlet obstruction. It has been postulated that inflammation induces prostatic fibrosis but this relationship has...

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Main Authors:	Wong, Letitia, Hutson, Paul R., Bushman, Wade
Format:	Online
Language:	English
Published:	Public Library of Science 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4065064/

id	pubmed-4065064
recordtype	oai_dc
spelling	pubmed-40650642014-06-25 Prostatic Inflammation Induces Fibrosis in a Mouse Model of Chronic Bacterial Infection Wong, Letitia Hutson, Paul R. Bushman, Wade Research Article Inflammation of the prostate is strongly correlated with development of lower urinary tract symptoms and several studies have implicated prostatic fibrosis in the pathogenesis of bladder outlet obstruction. It has been postulated that inflammation induces prostatic fibrosis but this relationship has never been tested. Here, we characterized the fibrotic response to inflammation in a mouse model of chronic bacterial-induced prostatic inflammation. Transurethral instillation of the uropathogenic E. coli into C3H/HeOuJ male mice induced persistent prostatic inflammation followed by a significant increase in collagen deposition and hydroxyproline content. This fibrotic response to inflammation was accompanied with an increase in collagen synthesis determined by the incorporation of 3H-hydroxyproline and mRNA expression of several collagen remodeling-associated genes, including Col1a1, Col1a2, Col3a1, Mmp2, Mmp9, and Lox. Correlation analysis revealed a positive correlation of inflammation severity with collagen deposition and immunohistochemical staining revealed that CD45+VIM+ fibrocytes were abundant in inflamed prostates at the time point coinciding with increased collagen synthesis. Furthermore, flow cytometric analysis demonstrated an increased percentage of these CD45+VIM+ fibrocytes among collagen type I expressing cells. These data show–for the first time–that chronic prostatic inflammation induces collagen deposition and implicates fibrocytes in the fibrotic process. Public Library of Science 2014-06-20 /pmc/articles/PMC4065064/ /pubmed/24950301 http://dx.doi.org/10.1371/journal.pone.0100770 Text en © 2014 Wong et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Wong, Letitia Hutson, Paul R. Bushman, Wade
spellingShingle	Wong, Letitia Hutson, Paul R. Bushman, Wade Prostatic Inflammation Induces Fibrosis in a Mouse Model of Chronic Bacterial Infection
author_facet	Wong, Letitia Hutson, Paul R. Bushman, Wade
author_sort	Wong, Letitia
title	Prostatic Inflammation Induces Fibrosis in a Mouse Model of Chronic Bacterial Infection
title_short	Prostatic Inflammation Induces Fibrosis in a Mouse Model of Chronic Bacterial Infection
title_full	Prostatic Inflammation Induces Fibrosis in a Mouse Model of Chronic Bacterial Infection
title_fullStr	Prostatic Inflammation Induces Fibrosis in a Mouse Model of Chronic Bacterial Infection
title_full_unstemmed	Prostatic Inflammation Induces Fibrosis in a Mouse Model of Chronic Bacterial Infection
title_sort	prostatic inflammation induces fibrosis in a mouse model of chronic bacterial infection
description	Inflammation of the prostate is strongly correlated with development of lower urinary tract symptoms and several studies have implicated prostatic fibrosis in the pathogenesis of bladder outlet obstruction. It has been postulated that inflammation induces prostatic fibrosis but this relationship has never been tested. Here, we characterized the fibrotic response to inflammation in a mouse model of chronic bacterial-induced prostatic inflammation. Transurethral instillation of the uropathogenic E. coli into C3H/HeOuJ male mice induced persistent prostatic inflammation followed by a significant increase in collagen deposition and hydroxyproline content. This fibrotic response to inflammation was accompanied with an increase in collagen synthesis determined by the incorporation of 3H-hydroxyproline and mRNA expression of several collagen remodeling-associated genes, including Col1a1, Col1a2, Col3a1, Mmp2, Mmp9, and Lox. Correlation analysis revealed a positive correlation of inflammation severity with collagen deposition and immunohistochemical staining revealed that CD45+VIM+ fibrocytes were abundant in inflamed prostates at the time point coinciding with increased collagen synthesis. Furthermore, flow cytometric analysis demonstrated an increased percentage of these CD45+VIM+ fibrocytes among collagen type I expressing cells. These data show–for the first time–that chronic prostatic inflammation induces collagen deposition and implicates fibrocytes in the fibrotic process.
publisher	Public Library of Science
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4065064/
_version_	1612104224091406336

Prostatic Inflammation Induces Fibrosis in a Mouse Model of Chronic Bacterial Infection

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