Cargando…

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

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 wit...

Descripción completa

Detalles Bibliográficos
Autores principales: Tinazzi, Ilaria, Mulipa, Panji, Colato, Chiara, Abignano, Giuseppina, Ballarin, Andrea, Biasi, Domenico, Emery, Paul, Ross, Rebecca L., Del Galdo, Francesco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8706846/
https://www.ncbi.nlm.nih.gov/pubmed/34945116
http://dx.doi.org/10.3390/jcm10245820
_version_ 1784622291507740672
author Tinazzi, Ilaria
Mulipa, Panji
Colato, Chiara
Abignano, Giuseppina
Ballarin, Andrea
Biasi, Domenico
Emery, Paul
Ross, Rebecca L.
Del Galdo, Francesco
author_facet Tinazzi, Ilaria
Mulipa, Panji
Colato, Chiara
Abignano, Giuseppina
Ballarin, Andrea
Biasi, Domenico
Emery, Paul
Ross, Rebecca L.
Del Galdo, Francesco
author_sort Tinazzi, Ilaria
collection PubMed
description 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.
format Online
Article
Text
id pubmed-8706846
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-87068462021-12-25 SFRP4 Expression Is Linked to Immune-Driven Fibrotic Conditions, Correlates with Skin and Lung Fibrosis in SSc and a Potential EMT Biomarker Tinazzi, Ilaria Mulipa, Panji Colato, Chiara Abignano, Giuseppina Ballarin, Andrea Biasi, Domenico Emery, Paul Ross, Rebecca L. Del Galdo, Francesco J Clin Med Article 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. MDPI 2021-12-13 /pmc/articles/PMC8706846/ /pubmed/34945116 http://dx.doi.org/10.3390/jcm10245820 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tinazzi, Ilaria
Mulipa, Panji
Colato, Chiara
Abignano, Giuseppina
Ballarin, Andrea
Biasi, Domenico
Emery, Paul
Ross, Rebecca L.
Del Galdo, Francesco
SFRP4 Expression Is Linked to Immune-Driven Fibrotic Conditions, Correlates with Skin and Lung Fibrosis in SSc and a Potential EMT Biomarker
title SFRP4 Expression Is Linked to Immune-Driven Fibrotic Conditions, Correlates with Skin and Lung Fibrosis in SSc and a Potential EMT Biomarker
title_full SFRP4 Expression Is Linked to Immune-Driven Fibrotic Conditions, Correlates with Skin and Lung Fibrosis in SSc and a Potential EMT Biomarker
title_fullStr SFRP4 Expression Is Linked to Immune-Driven Fibrotic Conditions, Correlates with Skin and Lung Fibrosis in SSc and a Potential EMT Biomarker
title_full_unstemmed SFRP4 Expression Is Linked to Immune-Driven Fibrotic Conditions, Correlates with Skin and Lung Fibrosis in SSc and a Potential EMT Biomarker
title_short SFRP4 Expression Is Linked to Immune-Driven Fibrotic Conditions, Correlates with Skin and Lung Fibrosis in SSc and a Potential EMT Biomarker
title_sort sfrp4 expression is linked to immune-driven fibrotic conditions, correlates with skin and lung fibrosis in ssc and a potential emt biomarker
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8706846/
https://www.ncbi.nlm.nih.gov/pubmed/34945116
http://dx.doi.org/10.3390/jcm10245820
work_keys_str_mv AT tinazziilaria sfrp4expressionislinkedtoimmunedrivenfibroticconditionscorrelateswithskinandlungfibrosisinsscandapotentialemtbiomarker
AT mulipapanji sfrp4expressionislinkedtoimmunedrivenfibroticconditionscorrelateswithskinandlungfibrosisinsscandapotentialemtbiomarker
AT colatochiara sfrp4expressionislinkedtoimmunedrivenfibroticconditionscorrelateswithskinandlungfibrosisinsscandapotentialemtbiomarker
AT abignanogiuseppina sfrp4expressionislinkedtoimmunedrivenfibroticconditionscorrelateswithskinandlungfibrosisinsscandapotentialemtbiomarker
AT ballarinandrea sfrp4expressionislinkedtoimmunedrivenfibroticconditionscorrelateswithskinandlungfibrosisinsscandapotentialemtbiomarker
AT biasidomenico sfrp4expressionislinkedtoimmunedrivenfibroticconditionscorrelateswithskinandlungfibrosisinsscandapotentialemtbiomarker
AT emerypaul sfrp4expressionislinkedtoimmunedrivenfibroticconditionscorrelateswithskinandlungfibrosisinsscandapotentialemtbiomarker
AT rossrebeccal sfrp4expressionislinkedtoimmunedrivenfibroticconditionscorrelateswithskinandlungfibrosisinsscandapotentialemtbiomarker
AT delgaldofrancesco sfrp4expressionislinkedtoimmunedrivenfibroticconditionscorrelateswithskinandlungfibrosisinsscandapotentialemtbiomarker