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Further evidence of the involvement of the Wnt signaling pathway in Dupuytren’s disease
Genetic background plays an important role in the development of Dupuytren’s disease. A genome-wide association study (GWAS) showed that nine loci are associated with the disease, six of which contain genes that are involved in Wnt signaling (WNT2, WNT4, WNT7B, RSPO2, SFRP4, SULF1). To obtain insigh...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Netherlands
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4850140/ https://www.ncbi.nlm.nih.gov/pubmed/26635199 http://dx.doi.org/10.1007/s12079-015-0312-8 |
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author | ten Dam, Evert-Jan P. M. van Beuge, Marike M. Bank, Ruud A. Werker, Paul M. N. |
author_facet | ten Dam, Evert-Jan P. M. van Beuge, Marike M. Bank, Ruud A. Werker, Paul M. N. |
author_sort | ten Dam, Evert-Jan P. M. |
collection | PubMed |
description | Genetic background plays an important role in the development of Dupuytren’s disease. A genome-wide association study (GWAS) showed that nine loci are associated with the disease, six of which contain genes that are involved in Wnt signaling (WNT2, WNT4, WNT7B, RSPO2, SFRP4, SULF1). To obtain insight in the role of these genes, we performed expression studies on affected and unaffected patient’s tissues. Surgically obtained nodules and cords from eight Dupuytren’s patients were compared to patient-matched control tissue (unaffected transverse palmar fascia). The Wnt-related genes found in the GWAS, the classical Wnt-downstream protein β-catenin, as well as (myo)fibroblast markers were analyzed using real-time qPCR and immunohistochemical stainings for mRNA levels and protein levels, respectively. The collagen-coding genes COL1A1 and COL3A1 were highly upregulated on mRNA level, both in cords and nodules. Three Wnt-related genes were found to be differently regulated compared to control tissue: WNT2 was downregulated in nodules, WNT7B was upregulated in nodules, and SFRP4 was upregulated in nodules and cords. Immunohistochemistry revealed significantly less staining of Wnt2 in cords, but significantly more staining for Wnt7b in nodules. There was significantly more staining of α-SMA in nodules and cord and β-catenin in nodules than in control tissue. We found differences in expression, both at mRNA and protein level, in several Wnt-related genes found earlier to be associated with Dupuytren’s disease. Of these, Wnt7b was upregulated and found in close association with both α-SMA and β-catenin expressing cells, making it a candidate pro-fibrotic mediator in Dupuytren’s disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12079-015-0312-8) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4850140 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Springer Netherlands |
record_format | MEDLINE/PubMed |
spelling | pubmed-48501402016-05-16 Further evidence of the involvement of the Wnt signaling pathway in Dupuytren’s disease ten Dam, Evert-Jan P. M. van Beuge, Marike M. Bank, Ruud A. Werker, Paul M. N. J Cell Commun Signal Research Article Genetic background plays an important role in the development of Dupuytren’s disease. A genome-wide association study (GWAS) showed that nine loci are associated with the disease, six of which contain genes that are involved in Wnt signaling (WNT2, WNT4, WNT7B, RSPO2, SFRP4, SULF1). To obtain insight in the role of these genes, we performed expression studies on affected and unaffected patient’s tissues. Surgically obtained nodules and cords from eight Dupuytren’s patients were compared to patient-matched control tissue (unaffected transverse palmar fascia). The Wnt-related genes found in the GWAS, the classical Wnt-downstream protein β-catenin, as well as (myo)fibroblast markers were analyzed using real-time qPCR and immunohistochemical stainings for mRNA levels and protein levels, respectively. The collagen-coding genes COL1A1 and COL3A1 were highly upregulated on mRNA level, both in cords and nodules. Three Wnt-related genes were found to be differently regulated compared to control tissue: WNT2 was downregulated in nodules, WNT7B was upregulated in nodules, and SFRP4 was upregulated in nodules and cords. Immunohistochemistry revealed significantly less staining of Wnt2 in cords, but significantly more staining for Wnt7b in nodules. There was significantly more staining of α-SMA in nodules and cord and β-catenin in nodules than in control tissue. We found differences in expression, both at mRNA and protein level, in several Wnt-related genes found earlier to be associated with Dupuytren’s disease. Of these, Wnt7b was upregulated and found in close association with both α-SMA and β-catenin expressing cells, making it a candidate pro-fibrotic mediator in Dupuytren’s disease. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12079-015-0312-8) contains supplementary material, which is available to authorized users. Springer Netherlands 2015-12-03 2016-03 /pmc/articles/PMC4850140/ /pubmed/26635199 http://dx.doi.org/10.1007/s12079-015-0312-8 Text en © The Author(s) 2015 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Research Article ten Dam, Evert-Jan P. M. van Beuge, Marike M. Bank, Ruud A. Werker, Paul M. N. Further evidence of the involvement of the Wnt signaling pathway in Dupuytren’s disease |
title | Further evidence of the involvement of the Wnt signaling pathway in Dupuytren’s disease |
title_full | Further evidence of the involvement of the Wnt signaling pathway in Dupuytren’s disease |
title_fullStr | Further evidence of the involvement of the Wnt signaling pathway in Dupuytren’s disease |
title_full_unstemmed | Further evidence of the involvement of the Wnt signaling pathway in Dupuytren’s disease |
title_short | Further evidence of the involvement of the Wnt signaling pathway in Dupuytren’s disease |
title_sort | further evidence of the involvement of the wnt signaling pathway in dupuytren’s disease |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4850140/ https://www.ncbi.nlm.nih.gov/pubmed/26635199 http://dx.doi.org/10.1007/s12079-015-0312-8 |
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