THU0012 Observing Dysregulation of Signal Transduction Genes in the WNT Pathway Using two Methods: Table 1
| العنوان: | THU0012 Observing Dysregulation of Signal Transduction Genes in the WNT Pathway Using two Methods: Table 1 |
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| المؤلفون: | Jacqueline Frost, Mohammed Tikly, K. Rabionet, Xavier Estivill, Michèle Ramsay |
| المصدر: | Annals of the Rheumatic Diseases. 74:197.1-197 |
| بيانات النشر: | BMJ, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Genetics, Frizzled, FZD4, Immunology, Wnt signaling pathway, Biology, General Biochemistry, Genetics and Molecular Biology, Rheumatology, Frzb, Secreted frizzled-related protein 1, Gene expression, Immunology and Allergy, Signal transduction, Morphogen |
| الوصف: | Background In recent years, the morphogen pathways (1), and specifically the Wnt pathway has been implicated in the development of fibrosis in Systemic Sclerosis (SSc) (2). Animal studies have shown that dysregulation frizzled related protein ( FRZB ) (3), frizzled class receptor 4 ( FZD4 ) (4) and secreted frizzled related protein 1 ( SFRP1 ) (5) have been implicated in the pathogenesis of SSc. Objectives Examine differential gene expression and methylation status of 84 genes in the Wnt pathway. Methods Skin biopsies were taken from 8 black South African patients with early ( 2 Profiler and Epitect Methyl qPCR Arrays, as well as mRNA-sequencing. Data was analysed using HTqPCR and DESeq2. Results The expression data from the qPCR array suggests that the 8 patients are segregating into two groups, and that the most significantly expressed genes are involved in signal transduction within the Wnt pathway. Results can be seen in the table below. There was no significant difference in gene expression between Involved and Uninvolved skin samples. Analysis of the methylation status of 22 Wnt pathway genes revealed no significant results. Conclusions The results of this study suggest that the dysregulation of Wnt pathway signal transduction is involved in the development of fibrosis in SSc in humans. Interestingly, although patients are phenotypically similar, they are clustering into two distinct groups based on the differential expression of the Wnt pathway genes. Involved and Uninvolved skin exhibit similar magnitudes of expression. Identification of dysregulated genes in the pathway may provide novel insights into the pathogenesis of SSc and hence potential new targets for therapy. References Distler et al. (2014) Ann Rheum Dis. 73(6): 1265-8 Lafyatis (2012) Nat Rev Rheumatol. 8(8): 441-2 De Langhe et al. (2014) Fibrogenesis Tissue Repair. 7(14) Igota et al. (2013) Int J Med Sci. 10(4): 344-54 Dees et al. (2014) Ann Rheum Dis. 73(6): 1232-9 Acknowledgements 1. Wits-Novartis-CRG Scientist Exchange Program. 2. National Research Foundation South Africa. 3. Estivill Lab (CRG, Barcelona, Spain). 4. Frank Staedtler (Novartis, Basel, Switzerland. Disclosure of Interest None declared |
| تدمد: | 1468-2060 0003-4967 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::9bb12b601c06ab62053cc6b71e48871fTest https://doi.org/10.1136/annrheumdis-2015-eular.4452Test |
| رقم الانضمام: | edsair.doi...........9bb12b601c06ab62053cc6b71e48871f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14682060 00034967 |
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