Evidence map›Paper›PMID 39381224›Full record

ArticleHeliyon2024

Reduced WNT4 expression in normal skin fibroblasts leads to 'Dupuytren-like' changes in the transcriptome.

Aoife O'Brien, Andrew Stevenson, Lucy Barrett, Nicholas B Lawler, Nicole Hortin, Zhenjun Deng, Amira Allahham, Fabio Quondamatteo, Nicole Smith, K Swaminathan Iyer and 2 more

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Article in Heliyon, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

12 authors.

Aoife O'BrienDepartment of Anatomy and Regenerative Medicine, Royal College of Surgeons, Ireland.
Andrew StevensonBurn Injury Research Unit (BIRU), School of Biomedical Sciences, University of Western Australia, Australia.
Lucy BarrettBurn Injury Research Unit (BIRU), School of Biomedical Sciences, University of Western Australia, Australia.
Nicholas B LawlerSchool of Molecular Sciences, The University of Western Australia, Perth, WA, 6009, Australia.
Nicole HortinBurn Injury Research Unit (BIRU), School of Biomedical Sciences, University of Western Australia, Australia.
Zhenjun DengBurn Injury Research Unit (BIRU), School of Biomedical Sciences, University of Western Australia, Australia.
Amira AllahhamBurn Injury Research Unit (BIRU), School of Biomedical Sciences, University of Western Australia, Australia.
Fabio QuondamatteoDepartment of Anatomy and Regenerative Medicine, Royal College of Surgeons, Ireland.
Nicole SmithSchool of Molecular Sciences, The University of Western Australia, Perth, WA, 6009, Australia.
K Swaminathan IyerSchool of Molecular Sciences, The University of Western Australia, Perth, WA, 6009, Australia.
Fiona M WoodBurn Injury Research Unit (BIRU), School of Biomedical Sciences, University of Western Australia, Australia.
Mark W FearBurn Injury Research Unit (BIRU), School of Biomedical Sciences, University of Western Australia, Australia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Dupuytren's disease (DD) is a fibro-proliferative disorder of unknown aetiology. Previous studies have implicated multiple WNT signalling genes/proteins in Dupuytren pathology, including WNT4. However, it is not yet clear whether WNT signalling dysregulation plays an important role in the initiation of the disease or progression. The aim of this study was to determine if loss of WNT4 expression triggered 'Dupuytren-like' changes in the transcriptome of healthy skin fibroblasts. Methods: Fibroblasts were isolated from the wrists of healthy adult males and from the wrists and disease cord tissue from males in a family positive for Dupuytren's disease. Normal skin fibroblasts from healthy controls were treated with WNT4 siRNA and scrambled controls. RNASeq was used to analyse the transcriptomes of disease and non-disease fibroblasts from patients with Dupuytren's as well as in siRNA treated and non-treated control fibroblasts. Results: Analysis of the transcriptomes from DD patient and normal skin fibroblasts showed significant differences, including in WNT4 expression. Downregulation of WNT4 in normal skin fibroblasts using siRNA led to 'DD-like' changes in the transcriptome. Conclusion: In people susceptible to DD WNT4 is downregulated even in non-fibrotic fibroblasts. Knockdown of WNT4 in normal fibroblasts led to changes that made cells 'DD-like'. This study shows that WNT4 is down regulated in 'non-disease' cells, and that downregulating WNT4 in normal skin fibroblasts leads to widespread 'DD like' changes in the transcriptome, suggesting WNT4 downregulation is a key driver of DD.

Identifiers

PMID39381224
PMCPMC11458971

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