{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T13:59:27Z","timestamp":1781013567229,"version":"3.54.1"},"reference-count":34,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T00:00:00Z","timestamp":1639353600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>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 TGF\u03b2-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.<\/jats:p>","DOI":"10.3390\/jcm10245820","type":"journal-article","created":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T01:20:41Z","timestamp":1639444841000},"page":"5820","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["SFRP4 Expression Is Linked to Immune-Driven Fibrotic Conditions, Correlates with Skin and Lung Fibrosis in SSc and a Potential EMT Biomarker"],"prefix":"10.3390","volume":"10","author":[{"given":"Ilaria","family":"Tinazzi","sequence":"first","affiliation":[{"name":"Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds LS7 9TF, UK"},{"name":"Unit of Rheumatology, IRCSS Ospedale Sacro Cuore-Don Calabria, 37024 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panji","family":"Mulipa","sequence":"additional","affiliation":[{"name":"Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds LS7 9TF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Colato","sequence":"additional","affiliation":[{"name":"Section of Pathology, Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1479-0133","authenticated-orcid":false,"given":"Giuseppina","family":"Abignano","sequence":"additional","affiliation":[{"name":"Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds LS7 9TF, UK"},{"name":"NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds LS7 4SA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Ballarin","sequence":"additional","affiliation":[{"name":"Department of Surgery, University Hospital of Verona, 37126 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Biasi","sequence":"additional","affiliation":[{"name":"Unit of Rheumatology, University Hospital of Verona, 37126 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Emery","sequence":"additional","affiliation":[{"name":"Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds LS7 9TF, UK"},{"name":"NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds LS7 4SA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7750-4280","authenticated-orcid":false,"given":"Rebecca L.","family":"Ross","sequence":"additional","affiliation":[{"name":"Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds LS7 9TF, UK"},{"name":"NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds LS7 4SA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8528-2283","authenticated-orcid":false,"given":"Francesco","family":"Del Galdo","sequence":"additional","affiliation":[{"name":"Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds LS7 9TF, UK"},{"name":"NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds LS7 4SA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/ncprheum0115","article-title":"Mechanisms and consequences of fibrosis in systemic sclerosis","volume":"2","author":"Denton","year":"2006","journal-title":"Nat. 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