| Bladder outlet obstruction: progression from inflammation to fibrosis. | |
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MedLine Citation:
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PMID: 20590549 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: To investigate the progression of urodynamic changes, as well as histological and biochemical outcomes over a prolonged period of partial bladder outlet obstruction (pBOO) in an animal model with physiologically relevant pBOO. MATERIALS AND METHODS: Healthy, adult, female Fischer rats underwent surgical creation of a pBOO for either 2, 4, 8, or 13 weeks and were compared with sham-operated rats. Urodynamic measurements were used to compare bladder volumes and pressure. Tissue was grossly analysed with light microscopy and bladder weights and thicknesses were compared. Reverse transcription-polymerase chain reaction for collagen, transforming growth factor β (TGF-β), connective tissue growth factor (CTGF), hypoxia inducible factor 1α (HIF-1α), and platelet-derived growth factor (PDGF-A) was performed on all samples, as well as immunohistochemistry (IHC) for α-smooth muscle actin (α-SMA). Finally, mass spectrometry was used to quantify the collagen content of the bladders as a measure of fibrosis. RESULTS: After induction of pBOO, all rats remained healthy. Initial urodynamics showed an increase in capacity while maintaining normal pressures, but then deteriorated into small capacity, high-pressure bladders. Haematoxylin and eosin (H&E) staining showed an initial inflammatory response, and this was confirmed with significantly increased mRNA levels of TGF-β, CTGF, HIF-1α, and PDGF. The progression to smooth muscle hypertrophy was evident on H&E and confirmed with increased bladder mass and thickness. IHC for α-SMA showed a progressive increase associated with the elevated bladder pressures. Masson's trichrome and mass spectrometry showed a progressive increase in collagen to 13 weeks. CONCLUSION: With this model, we have effectively replicated the clinical scenario, with significant pathophysiological changes occurring insidiously in otherwise healthy rats. We believe that our observed changes represent distinct phases of bladder decompensation; with an initial inflammatory response to the stress of the pBOO, smooth muscle hypertrophy to overcome the increased urethral resistance, and eventual decompensation to fibrosis. The time course of the inflammatory markers implies the need for early intervention to prevent this cascade. Novel strategies targeting these observed physiological responses could lead to improved preventative strategies, with respect to biochemical pathways and the time course of their initiation. |
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Authors:
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Peter D Metcalfe; JianFei Wang; Haiyan Jiao; Yue Huang; Keijiro Hori; Ronald B Moore; Edward E Tredget |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: BJU international Volume: 106 ISSN: 1464-410X ISO Abbreviation: BJU Int. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-16 Completed Date: 2011-01-04 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100886721 Medline TA: BJU Int Country: England |
Other Details:
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Languages: eng Pagination: 1686-94 Citation Subset: IM |
Copyright Information:
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© 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL. |
Affiliation:
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Division of Paediatric Surgery, Department of Surgery, University of Alberta, Edmonton, Alberta, Canada. pmetcalf@ualberta.ca |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Collagen / metabolism Connective Tissue Growth Factor / metabolism Cystitis / pathology Disease Models, Animal Disease Progression Female Fibrosis Hypoxia-Inducible Factor 1, alpha Subunit / metabolism Immunohistochemistry Muscle, Smooth / pathology* Platelet-Derived Growth Factor / metabolism Rats Rats, Inbred F344 Reverse Transcriptase Polymerase Chain Reaction Transforming Growth Factor beta / metabolism Urinary Bladder / pathology* Urinary Bladder Neck Obstruction / pathology* Urodynamics |
| Grant Support | |
ID/Acronym/Agency:
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//Canadian Institutes of Health Research |
| Chemical | |
Reg. No./Substance:
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0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Platelet-Derived Growth Factor; 0/Transforming Growth Factor beta; 0/platelet-derived growth factor A; 139568-91-5/Connective Tissue Growth Factor; 9007-34-5/Collagen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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