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MiRNA Let-7a and Let-7d Are Induced by Globotriaosylceramide via NF-kB Activation in Fabry Disease
- Source :
- Genes, Vol 12, Iss 8, p 1184 (2021)
- Publication Year :
- 2021
- Publisher :
- MDPI AG, 2021.
-
Abstract
- Background: Fabry disease is a hereditary genetic defect resulting in reduced activity of the enzyme α-galactosidase-A and the accumulation of globotriaosylceramide (Gb3) in body fluids and cells. Gb3 accumulation was especially reported for the vascular endothelium in several organs. Methods: Three Fabry disease patients were screened using a micro-RNA screen. An in vitro approach in human endothelial cells was used to determine miRNA regulation by Gb3. Results: In a micro-RNA screen of three Fabry patients undergoing enzyme replacement therapy, we found that miRNAs let-7a and let-7d were significantly increased after therapy. We demonstrate in vitro in endothelial cells that Gb3 induced activation of NF-κB and activated downstream targets. In addition, NF-κB activity directly reduced let-7a and let-7d miRNA expression as inhibiting NF-kB nuclear entry abolished the Gb3 effects. Conclusion: We suggest that let-7a and let-7d are potential markers for enzyme activity and inflammation in Fabry disease patients.
- Subjects :
- Fabry disease
Gb3
NF-κB
inflammation
Genetics
QH426-470
Subjects
Details
- Language :
- English
- ISSN :
- 20734425
- Volume :
- 12
- Issue :
- 8
- Database :
- Directory of Open Access Journals
- Journal :
- Genes
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.635a03a757aa41129cdf7d63e005b7c4
- Document Type :
- article
- Full Text :
- https://doi.org/10.3390/genes12081184