Related Experiment Video
Updated: Feb 5, 2026
Imaging Features of Systemic Sclerosis-Associated Interstitial Lung Disease
Published on: June 16, 2020
Dysregulation of the Wnt signaling pathway in South African patients with diffuse systemic sclerosis
Jacqueline Frost1,2, Xavier Estivill3,4,5, Michèle Ramsay6,7
1Division of Human Genetics, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2001, South Africa. Jacqueline.frost@mssm.edu.
Abstract:
The objective was to explore changes in gene expression in Wnt pathway genes in skin samples of black South Africans with diffuse cutaneous systemic sclerosis (dcSSc). Affected (forearm) and unaffected (upper back) skin samples of eight Black South Africans with active early dcSSc were compared to skin samples from seven ethnically matched control subjects. The Wnt Pathway Plus RT2 Profiler qPCR Array was used to determine gene expression and analyzed for differential expression between cases and controls. Selective validation was done using single-gene TaqMan assays. Several genes were similarly upregulated in both affected and unaffected skin of the dcSSc patients compared to controls. These included the Wnt ligands WNT7A and WNT10A, the frizzled receptors FZD8 and FZD9, intracellular signaling proteins AXIN1 and AXIN2, and the pathway target genes FGF4 and MMP7. Principal component analysis revealed patients clustering into two groups, which co-segregated with clinical features of interstitial lung disease and/or inflammatory myopathy, or the absence of an inflammation phenotype. These two groups showed paradoxical gene expression of the genes TCF7, SOX17, and FRZB in affected and unaffected skin. This study provides further evidence of dysregulation of gene expression at various levels of the Wnt signaling pathway in dcSSc. Moreover, principal component analysis showed two distinct patient clusters of gene expression, which co-segregated with the presence or absence of clinical inflammatory features, and may reflect different pathological pathways in dcSSc.
Insights
Gene expression in the Wnt signaling pathway is altered in diffuse cutaneous systemic sclerosis (dcSSc) patients. Two patient groups emerged based on gene expression patterns, correlating with distinct clinical inflammatory features.
Area of Science:
- Genetics
- Dermatology
- Immunology
Background:
- Diffuse cutaneous systemic sclerosis (dcSSc) is an autoimmune disease characterized by skin thickening and potential organ involvement.
- The Wnt signaling pathway plays a crucial role in embryonic development and tissue homeostasis, and its dysregulation is implicated in various diseases.
- Understanding gene expression changes in dcSSc is vital for identifying potential therapeutic targets.
Purpose of the Study:
- To investigate differential gene expression within the Wnt signaling pathway in skin samples from Black South African patients with diffuse cutaneous systemic sclerosis (dcSSc).
- To identify specific Wnt pathway genes that are altered in affected and unaffected skin of dcSSc patients compared to healthy controls.
- To explore potential correlations between gene expression patterns and clinical phenotypes in dcSSc.
Main Methods:
- Comparison of gene expression in affected (forearm) and unaffected (upper back) skin samples from eight dcSSc patients and seven ethnically matched controls.
- Utilized the Wnt Pathway Plus RT2 Profiler qPCR Array for broad gene expression analysis.
- Employed TaqMan assays for selective validation of differentially expressed genes.
- Applied Principal Component Analysis (PCA) to identify patient clusters based on gene expression profiles.
Main Results:
- Several Wnt pathway genes, including ligands (WNT7A, WNT10A), receptors (FZD8, FZD9), signaling proteins (AXIN1, AXIN2), and target genes (FGF4, MMP7), were upregulated in both affected and unaffected skin of dcSSc patients compared to controls.
- PCA revealed two distinct clusters of dcSSc patients based on gene expression patterns.
- These patient clusters correlated with the presence or absence of clinical features such as interstitial lung disease, inflammatory myopathy, or a general inflammation phenotype.
- Differential expression of TCF7, SOX17, and FRZB was observed between these two patient clusters.
Conclusions:
- The study confirms significant dysregulation of Wnt signaling pathway genes in dcSSc.
- Distinct gene expression profiles in dcSSc patients suggest the existence of at least two underlying pathological pathways.
- These findings highlight the potential of Wnt pathway modulation as a therapeutic strategy for specific dcSSc patient subgroups.
Related Concept Videos
02:54Canonical Wnt Signaling Pathway
01:41Non-Canonical Wnt Signaling Pathways
03:14Notch Signaling Pathway
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
02:33Hedgehog Signaling Pathway
01:19Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
02:26NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...