Secreted
Frizzled Receptor Protein 4 (SFRP4) has been shown to be increased in Scleroderma (SSc). To determine its role in immune-driven
fibrosis, we analysed SSc and sclerotic
Chronic Graft Versus Host Disease (sclGVHD) biosamples; skin biopsies (n = 24) from chronic GVHD patients (8 with and 5 without sclGVHD), 8 from SSc and 3 healthy controls (HC) were analysed by immunofluorescence (IF) and SSc patient sera (n = 77) assessed by ELISA. Epithelial cell lines used for in vitro Epithelial-Mesenchymal-Transition (EMT) assays and analysed by Western Blot, RT-PCR and immunofluorescence. SclGVHD skin biopsies resembled pathologic features of SSc. IF of fibrotic skin biopsies indicated the major source of SFRP4 expression were dermal fibroblasts, melanocytes and
vimentin positive/
caveolin-1 negative cells in the basal layer of the epidermis. In vitro studies showed increased
vimentin and SFRP4 expression accompanied with decreased
caveolin-1 expression during TGFβ-induced EMT. Additionally, SFRP4 serum concentration correlated with severity of lung and skin
fibrosis in SSc. In conclusion, SFRP4 expression is increased during skin
fibrosis in two different immune-driven conditions, and during an in vitro EMT model. Its serum levels correlate with skin and lung
fibrosis in SSc and may function as
biomarker of EMT. Further studies are warranted to elucidate the role of SFRP4 in EMT within the pathogenesis of tissue
fibrosis.