title: Increased CCT-eta expression is a marker of latent and active disease and a modulator of fibroblast contractility in Dupuytren's contracture.
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.
authors.affiliation: Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: Latha
authors.initials: L
authors.lastname: Satish
authors.forename: David B
authors.initials: DB
authors.lastname: O'Gorman
authors.forename: Sandra
authors.initials: S
authors.lastname: Johnson
authors.forename: Christina
authors.initials: C
authors.lastname: Raykha
authors.forename: Bing Siang
authors.initials: BS
authors.lastname: Gan
authors.forename: James H-C
authors.initials: JH
authors.lastname: Wang
authors.forename: Sandeep
authors.initials: S
authors.lastname: Kathju
mesh_terms: D000199:Actins / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D056404:Chaperonin Containing TCP-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D004387:Dupuytren Contracture / Q000378:metabolism / Q000473:pathology; D005205:Fascia / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D006801:Humans; D009119:Muscle Contraction / Q000502:physiology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D015415:Biomarkers; D034741:RNA, Small Interfering; D056404:Chaperonin Containing TCP-1