| Increased CCT-eta expression is a marker of latent and active disease and a modulator of fibroblast contractility in Dupuytren's contracture. | |
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MedLine Citation:
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PMID: 23292503 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Dupuytren's contracture (DC) is a fibroproliferative disorder of unknown etiology characterized by a scar-like contracture that develops in the palm and/or digits. We have previously reported that the eta subunit of the chaperonin containing T-complex polypeptide (CCT-eta) is increased in fibrotic wound healing, and is essential for the accumulation of α-smooth muscle actin (α-SMA) in fibroblasts. The purpose of this study was to determine if CCT-eta is similarly implicated in the aberrant fibrosis seen in DC and to investigate the role of CCT-eta in the behavior of myo/fibroblasts in DC. Fibroblasts were obtained from DC-affected palmar fascia, from adjacent phenotypically normal palmar fascia in the same DC patients (PF), and from non-DC palmar fascial tissues in patients undergoing carpal tunnel (CT) release. Inherent contractility in these three populations was examined using fibroblast-populated collagen lattices (FPCLs) and by cell traction force microscopy. Expression of CCT-eta and α-SMA protein was determined by Western blot. The effect of CCT-eta inhibition on the contractility of DC cells was determined by deploying an siRNA versus CCT-eta. DC cells were significantly more contractile than both matching palmar fascial (PF) cells and CT cells in both assays, with PF cells demonstrating an intermediate contractility in the FPCL assay. Whereas α-SMA protein was significantly increased only in DC cells compared to PF and CT cells, CCT-eta protein was significantly increased in both PF and DC cells compared to CT cells. siRNA-mediated depletion of CCT-eta inhibited the accumulation of both CCT-eta and α-SMA protein in DC cells, and also significantly decreased the contractility of treated DC cells. These observations suggest that increased expression of CCT-eta appears to be a marker for latent and active disease in these patients and to be essential for the increased contractility exhibited by these fibroblasts. |
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Authors:
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Latha Satish; David B O'Gorman; Sandra Johnson; Christina Raykha; Bing Siang Gan; James H-C Wang; Sandeep Kathju |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2013-1-6 |
Journal Detail:
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Title: Cell stress & chaperones Volume: - ISSN: 1466-1268 ISO Abbreviation: Cell Stress Chaperones Publication Date: 2013 Jan |
Date Detail:
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Created Date: 2013-1-7 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9610925 Medline TA: Cell Stress Chaperones Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA, 15213, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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