Dysregulation of the Wnt signaling pathway in South African patients with diffuse systemic sclerosis

Clinical Rheumatology
Jacqueline FrostMohammed Tikly

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...Continue Reading

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Citations

Jun 21, 2020·Current Rheumatology Reports·Monique Hinchcliff, Steven O'Reilly
Oct 4, 2020·Expert Review of Clinical Pharmacology·Bénédict Fallet, Ulrich A Walker
Mar 4, 2021·Liver International : Official Journal of the International Association for the Study of the Liver·Tatjana Seitz, Claus Hellerbrand
Apr 12, 2021·Best Practice & Research. Clinical Rheumatology·Maria Martin-Lopez, Patricia E Carreira
Jun 30, 2021·The British Journal of Dermatology·B J DoolanJ A McGrath
May 17, 2021·The Journal of Rheumatology·Tatiana NevskayaSindhu R Johnson

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