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Article

SFRP4 Expression Is Linked to Immune-Driven Fibrotic Conditions, Correlates with Skin and Lung Fibrosis in SSc and a Potential EMT Biomarker

by
Ilaria Tinazzi
1,2,
Panji Mulipa
1,
Chiara Colato
3,
Giuseppina Abignano
1,4,
Andrea Ballarin
5,
Domenico Biasi
6,
Paul Emery
1,4,
Rebecca L. Ross
1,4,* and
Francesco Del Galdo
1,4,*
1
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds LS7 9TF, UK
2
Unit of Rheumatology, IRCSS Ospedale Sacro Cuore-Don Calabria, 37024 Verona, Italy
3
Section of Pathology, Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy
4
NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds LS7 4SA, UK
5
Department of Surgery, University Hospital of Verona, 37126 Verona, Italy
6
Unit of Rheumatology, University Hospital of Verona, 37126 Verona, Italy
*
Authors to whom correspondence should be addressed.
J. Clin. Med. 2021, 10(24), 5820; https://doi.org/10.3390/jcm10245820
Submission received: 18 November 2021 / Revised: 3 December 2021 / Accepted: 8 December 2021 / Published: 13 December 2021
(This article belongs to the Special Issue Systemic Sclerosis—Pathogenesis and Emerging Therapies)
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Abstract

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.
Keywords: systemic sclerosis; SFRP4; GVHD; fibrosis; wnt; caveolin-1 systemic sclerosis; SFRP4; GVHD; fibrosis; wnt; caveolin-1

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MDPI and ACS Style

Tinazzi, I.; Mulipa, P.; Colato, C.; Abignano, G.; Ballarin, A.; Biasi, D.; Emery, P.; Ross, R.L.; Del Galdo, F. SFRP4 Expression Is Linked to Immune-Driven Fibrotic Conditions, Correlates with Skin and Lung Fibrosis in SSc and a Potential EMT Biomarker. J. Clin. Med. 2021, 10, 5820. https://doi.org/10.3390/jcm10245820

AMA Style

Tinazzi I, Mulipa P, Colato C, Abignano G, Ballarin A, Biasi D, Emery P, Ross RL, Del Galdo F. SFRP4 Expression Is Linked to Immune-Driven Fibrotic Conditions, Correlates with Skin and Lung Fibrosis in SSc and a Potential EMT Biomarker. Journal of Clinical Medicine. 2021; 10(24):5820. https://doi.org/10.3390/jcm10245820

Chicago/Turabian Style

Tinazzi, Ilaria, Panji Mulipa, Chiara Colato, Giuseppina Abignano, Andrea Ballarin, Domenico Biasi, Paul Emery, Rebecca L. Ross, and Francesco Del Galdo. 2021. "SFRP4 Expression Is Linked to Immune-Driven Fibrotic Conditions, Correlates with Skin and Lung Fibrosis in SSc and a Potential EMT Biomarker" Journal of Clinical Medicine 10, no. 24: 5820. https://doi.org/10.3390/jcm10245820

APA Style

Tinazzi, I., Mulipa, P., Colato, C., Abignano, G., Ballarin, A., Biasi, D., Emery, P., Ross, R. L., & Del Galdo, F. (2021). SFRP4 Expression Is Linked to Immune-Driven Fibrotic Conditions, Correlates with Skin and Lung Fibrosis in SSc and a Potential EMT Biomarker. Journal of Clinical Medicine, 10(24), 5820. https://doi.org/10.3390/jcm10245820

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