دورية أكاديمية
Genome-wide expression analysis in a Fabry disease human podocyte cell line
| العنوان: | Genome-wide expression analysis in a Fabry disease human podocyte cell line |
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| المؤلفون: | Sarah Snanoudj, Céline Derambure, Cheng Zhang, Nguyen Thi Hai Yen, Céline Lesueur, Sophie Coutant, Lénaïg Abily-Donval, Stéphane Marret, Hong Yang, Adil Mardinoglu, Soumeya Bekri, Abdellah Tebani |
| المصدر: | Heliyon, Vol 10, Iss 14, Pp e34357- (2024) |
| بيانات النشر: | Elsevier, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Science (General) LCC:Social sciences (General) |
| مصطلحات موضوعية: | Fabry disease, RNAseq, Transcriptomics, Metabolic modeling, Systems biology, Podocyte, Science (General), Q1-390, Social sciences (General), H1-99 |
| الوصف: | Fabry disease (FD) is an X-linked lysosomal disease caused by an enzyme deficiency of alpha-galactosidase A (α-gal A). This deficiency leads to the accumulation of glycosphingolipids in lysosomes, resulting in a range of clinical symptoms. The complex pathogenesis of FD involves lysosomal dysfunction, altered autophagy, and mitochondrial abnormalities. Omics sciences, particularly transcriptomic analysis, comprehensively understand molecular mechanisms underlying diseases. This study focuses on genome-wide expression analysis in an FD human podocyte model to gain insights into the underlying mechanisms of podocyte dysfunction. Human control and GLA-edited podocytes were used. Gene expression data was generated using RNA-seq analysis, and differentially expressed genes were identified using DESeq2. Principal component analysis and Spearman correlation have explored gene expression trends. Functional enrichment and Reporter metabolite analyses were conducted to identify significantly affected metabolites and metabolic pathways. Differential expression analysis revealed 247 genes with altered expression levels in GLA-edited podocytes compared to control podocytes. Among these genes, 136 were underexpressed, and 111 were overexpressed in GLA-edited cells. Functional analysis of differentially expressed genes showed their involvement in various pathways related to oxidative stress, inflammation, fatty acid metabolism, collagen and extracellular matrix homeostasis, kidney injury, apoptosis, autophagy, and cellular stress response. The study provides insights into molecular mechanisms underlying Fabry podocyte dysfunction. Integrating transcriptomics data with genome-scale metabolic modeling further unveiled metabolic alterations in GLA-edited podocytes. This comprehensive approach contributes to a better understanding of Fabry disease and may lead to identifying new biomarkers and therapeutic targets for this rare lysosomal disorder. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2405-8440 74841335 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S240584402410388X; https://doaj.org/toc/2405-8440 |
| DOI: | 10.1016/j.heliyon.2024.e34357 |
| URL الوصول: | https://doaj.org/article/98f4d6744b8c48ab8fb74841335491bb |
| رقم الأكسشن: | edsdoj.98f4d6744b8c48ab8fb74841335491bb |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 24058440 74841335 |
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| DOI: | 10.1016/j.heliyon.2024.e34357 |