title: WT1 expression is increased in primary fibroblasts derived from Dupuytren's disease tissues.
abstract: Dupuytren's disease (DD) is a fibroproliferative and contractile fibrosis of the palmar fascia that, like all other heritable fibroses, is currently incurable. While DD is invariably benign, it exhibits some molecular similarities to malignant tumours, including increased levels of ß-catenin, onco-fetal fibronectin, periostin and insulin-like growth factor (IGF)-II. To gain additional insights into the pathogenesis of DD, we have assessed the expression of WT1, encoding Wilm's tumour 1, an established tumour biomarker that is syntenic with IGF2, the gene encoding IGF-II in humans. We found that WT1 expression is robustly and consistently up regulated in primary fibroblasts derived from the fibrotic palmar fascia of patients with DD (DD cells), whereas syngeneic fibroblasts derived from the macroscopically unaffected palmar fascia in these patients and allogeneic fibroblasts derived from normal palmar fascia exhibited very low or undetectable WT1 transcript levels. WT1 immunoreactivity was evident in a subset of cells in the fibrotic palmar fascia of patients with DD, but not in macroscopically unaffected palmar fascia. These findings identify WT1 expression as a novel biomarker of fibrotic palmar fascia and are consistent with the hypothesis that the pathogeneses of DD and malignant tumours have molecular similarities.
authors.affiliation: Cell & Molecular Biology Laboratory, Roth|McFarlane Hand & Upper Limb Centre, London, ON, Canada. jcrawfo9@uwo.ca.|Lawson Health Research Institute, 268 Grosvenor Street, Room E2-137, London, ON, Canada, N6A 4V2. jcrawfo9@uwo.ca.
authors.forename: Justin
authors.initials: J
authors.lastname: Crawford
authors.affiliation: Cell & Molecular Biology Laboratory, Roth|McFarlane Hand & Upper Limb Centre, London, ON, Canada. craykha@hotmail.com.|Lawson Health Research Institute, 268 Grosvenor Street, Room E2-137, London, ON, Canada, N6A 4V2. craykha@hotmail.com.
authors.forename: Christina
authors.initials: C
authors.lastname: Raykha
authors.affiliation: Department of Biochemistry, University of Western Ontario, London, ON, Canada. dcharle4@uwo.ca.
authors.forename: Daevina
authors.initials: D
authors.lastname: Charles
authors.affiliation: Cell & Molecular Biology Laboratory, Roth|McFarlane Hand & Upper Limb Centre, London, ON, Canada. bsgan@rogers.com.|Lawson Health Research Institute, 268 Grosvenor Street, Room E2-137, London, ON, Canada, N6A 4V2. bsgan@rogers.com.|Department of Surgery, University of Western Ontario, London, ON, Canada. bsgan@rogers.com.|Department of Medical Biophysics, University of Western Ontario, London, ON, Canada. bsgan@rogers.com.
authors.forename: Bing Siang
authors.initials: BS
authors.lastname: Gan
authors.affiliation: Cell & Molecular Biology Laboratory, Roth|McFarlane Hand & Upper Limb Centre, London, ON, Canada. dogorman@uwo.ca.|Lawson Health Research Institute, 268 Grosvenor Street, Room E2-137, London, ON, Canada, N6A 4V2. dogorman@uwo.ca.|Department of Surgery, University of Western Ontario, London, ON, Canada. dogorman@uwo.ca.|Department of Biochemistry, University of Western Ontario, London, ON, Canada. dogorman@uwo.ca.
authors.forename: David B
authors.initials: DB
authors.lastname: O'Gorman
keywords: Biomarker; Dupuytren’s disease; Fibrosis; Wilm’s tumor 1