AWT1 is Constantly Expressed in Palmar Fascia Fibrosis and Promotes a Pro-Inflammatory Milieu
Abstract
Palmar fascia fibrosis (Dupuytren’s disease or DD), can cause permanent palmar-digital contractures. There are currently no effective treatments for DD. We have previously reported a DD-associated increase in the expression of WT1, encoding a transcription factor, Wilms Tumor 1 (WT1). We demonstrate that fibroblasts derived from fibrotic palmar fascia of DD patients constantly express an isoform of WT1, AWT1, unlike syngeneic pre-fibrotic (PF) or allogeneic normal control (CT) fibroblasts that only express AWT1 in response to pro-inflammatory stimuli. Adenoviral transduction and constant expression of AWT1 in PF and CT fibroblasts induced the expression of genes encoding pro-inflammatory cytokines and cytokine receptors. Co-culturing AWT1 expressing PF and CT fibroblasts with a monocyte cell line, THP-1, induced pro-inflammatory cytokine responses and the formation of a pro-inflammatory milieu. These data are consistent with the hypothesis that the constant expression of AWT1 in DD fibroblasts induces a local pro-inflammatory microenvironment that promotes fibrosis development.