| Wnt3a/β-catenin increases proliferation in heart valve interstitial cells. | |
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MedLine Citation:
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PMID: 22889676 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BACKGROUND: Valve interstitial cells (VICs), the most prevalent cells in the heart valve, mediate normal valve function and repair in valve injury and disease. The Wnt3a/β-catenin pathway, important for proliferation and endothelial-to-mesenchymal transition in endocardial cushion formation in valve development, is up-regulated in adult valves with calcific aortic stenosis. Therefore, we tested the hypothesis that Wnt3a/β-catenin signaling regulates proliferation in adult VICs. METHODS: Porcine VICs were treated with 150 ng/ml of exogenous Wnt3a. To measure proliferation, cells were counted on day 4 posttreatment and stained for bromodeoxyuridine (BrdU) at 24 h posttreatment. β-Catenin small interfering RNA (siRNA) was used to knock down β-catenin expression. Apoptosis was measured with terminal deoxynucleotidyl transferase dUTP nick end labeling assay. To assess changes in β-catenin, cells were stained for β-catenin at days 1, 3, 6, and 9 posttreatment. Western blot for β-catenin was performed on whole cell, cytoplasmic, and nuclear extracts at day 4 posttreatment. To measure β-catenin-mediated transcription, TOPFLASH/FOPFLASH reporter assay was performed at 24 h posttreatment. RESULTS: Wnt3a produced a significant increase in cell number at day 4 posttreatment and in the percentage of BrdU-positive nuclei at 24 h posttreatment. The increase in proliferation was abolished by β-catenin siRNA. Apoptosis was minimal in all conditions. Wnt3a produced progressively greater β-catenin staining as treatment length increased from 1 to 9 days. Wnt3a produced a significant increase in β-catenin protein in both whole cell and nuclear lysates after 4 days of treatment. Wnt3a significantly increased TOPFLASH/FOPFLASH reporter activity after 24 h of treatment. CONCLUSION: Wnt3a/β-catenin signaling pathway is an important regulator of proliferation in adult VICs. |
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Authors:
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Songyi Xu; Avrum I Gotlieb |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-8-10 |
Journal Detail:
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Title: Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology Volume: - ISSN: 1879-1336 ISO Abbreviation: Cardiovasc. Pathol. Publication Date: 2012 Aug |
Date Detail:
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Created Date: 2012-8-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9212060 Medline TA: Cardiovasc Pathol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2012 Elsevier Inc. All rights reserved. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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