SFRP4 Expression Is Linked to Immune-Driven Fibrotic Conditions, Correlates with Skin and Lung Fibrosis in SSc and a Potential EMT Biomarker.
Ilaria TinazziPanji MulipaChiara ColatoGiuseppina AbignanoAndrea BallarinDomenico BiasiPaul EmeryRebecca L RossFrancesco Del GaldoPublished in: Journal of clinical medicine (2021)
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.
Keyphrases
- epithelial mesenchymal transition
- poor prognosis
- soft tissue
- wound healing
- transforming growth factor
- binding protein
- systemic sclerosis
- signaling pathway
- long non coding rna
- squamous cell carcinoma
- case report
- ultrasound guided
- risk assessment
- radiation therapy
- lymph node
- rheumatoid arthritis
- small molecule
- cell death
- acute lymphoblastic leukemia
- endothelial cells
- idiopathic pulmonary fibrosis
- extracellular matrix
- amino acid
- diabetic rats
- high glucose
- case control