Cxcl-Type Chemokines−Induced Fibrosis In The Lower Urinary Tract

Gharaee−Kermani, Mehrnaz; Macoska, Jill A.

dc.contributor.author	Gharaee−Kermani, Mehrnaz
dc.contributor.author	Macoska, Jill A.
dc.date	2022-08-11T08:08:13.000
dc.date.accessioned	2022-08-23T15:46:48Z
dc.date.available	2022-08-23T15:46:48Z
dc.date.issued	2013-05-08
dc.date.submitted	2013-07-15
dc.identifier.doi	10.13028/8rx4-ky76
dc.identifier.uri	http://hdl.handle.net/20.500.14038/27835
dc.description	<p>Introduction: Recent studies from our group suggest that extracellular matrix (ECM) deposition and fibrosis characterize the peri−urethral prostate tissues of some men suffering from Lower Urinary Tract Symptoms (LUTS). Fibrosis can generally be regarded as an errant wound−healing process in response to chronic inflammation, and studies have shown that the aging prostate tissue microenvironment is rich with inflammatory cells and proteins. However, it is unclear whether these same inflammatory proteins, particularly CXC−type chemokines, can mediate myofibroblast phenoconversion and the ECM deposition necessary for the development of prostatic tissue fibrosis.</p> <p>Methods: Peri−urethral prostate tissues were disaggregated and subjected to FACS for expression of CD45 and collagen I. Primary stromal fibroblasts were cultured from explanted human peri−urethral prostatic tissues. N1 immortalized or primary prostate stromal fibroblasts were treated in serum−free defined media with TGF−β, CXCL5, CXCL8, or CXCL12 and evaluated using immunofluorescence or qRT−PCR for αSMA, collagen I, collagen III, vimentin, calponin, and tenascin protein and transcript expression, and by gel contraction assays for functional myofibroblast phenoconversion. The specificity of these responses to treatment with CXCL12 was assessed using a small molecule inhibitor, AMD3100, of the CXCL12 receptor, CXCR4.</p> <p>Results: The results of these studies showed that peri−urethral prostate tissues comprised both myofibroblastic and fibroblastic cell types, but that CD45+/collagen I+ fibrocytic cells were identified exclusively in peri−urethral tissues from men suffering from LUTS. Both N1 immortalized and primary prostate stromal fibroblasts exhibited complete and functional myofibroblast phenoconversion and were induced to express collagen I, collagen III and αSMA gene transcripts and proteins in response to treatment with CXC−type chemokines, even in the absence of exogenous TGF−β1.</p> <p>Conclusions: These findings suggest that CXC−type chemokines, particularly CXCL12, can efficiently and completely mediate myofibroblast phenoconversion and may thereby promote fibrotic changes in prostate tissue architecture associated with the development and progression of male lower urinary tract dysfunction.<br /><br /><br /></p>
dc.format	youtube
dc.language.iso	en_US
dc.rights	Copyright the Author(s)
dc.rights.uri	http://creativecommons.org/licenses/by-nc-sa/3.0/
dc.subject	Cell Biology
dc.subject	Male Urogenital Diseases
dc.subject	Translational Medical Research
dc.title	Cxcl-Type Chemokines−Induced Fibrosis In The Lower Urinary Tract
dc.type	Poster Abstract
dc.identifier.legacyfulltext	https://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1128&context=cts_retreat&unstamped=1
dc.identifier.legacycoverpage	https://escholarship.umassmed.edu/cts_retreat/2013/posters/53
dc.identifier.contextkey	4312042
refterms.dateFOA	2022-08-23T15:46:48Z
dc.identifier.submissionpath	cts_retreat/2013/posters/53