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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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Cell Stress and Chaperones Aims and scope

Abstract

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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Acknowledgments

We acknowledge the support of the Department of Plastic Surgery at the University of Pittsburgh Medical Center, and the Allegheny-Singer Research Institute. We gratefully acknowledge the funding support from NIH (AR049921 and AR06139) for this work (JHW). We would also like to thank Yan Wu, Department of Biochemistry, University of Western Ontario, for technical assistance.

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Authors and Affiliations

  1. Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA, 15213, USA

    Latha Satish & Sandeep Kathju

  2. Cell and Molecular Biology Laboratory of the Hand and Upper Limb Centre, St. Joseph’s Hospital, London, ON, Canada

    David B. O’Gorman, Christina Raykha & Bing Siang Gan

  3. Department of Surgery, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada

    David B. O’Gorman & Bing Siang Gan

  4. Center for Genomic Sciences, Allegheny-Singer Research Institute, Allegheny General Hospital, Pittsburgh, PA, 15212, USA

    Sandra Johnson

  5. The MechanoBiology Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh, Pittsburgh, PA, 15213, USA

    James H-C. Wang

Authors
  1. Latha Satish
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  2. David B. O’Gorman
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  3. Sandra Johnson
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  4. Christina Raykha
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  5. Bing Siang Gan
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  6. James H-C. Wang
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  7. Sandeep Kathju
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Correspondence to Sandeep Kathju.

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Satish, L., O’Gorman, D.B., Johnson, S. et al. Increased CCT-eta expression is a marker of latent and active disease and a modulator of fibroblast contractility in Dupuytren’s contracture. Cell Stress and Chaperones 18, 397–404 (2013). https://doi.org/10.1007/s12192-012-0392-9

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  • DOI: https://doi.org/10.1007/s12192-012-0392-9

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