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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 1184, p 1184 (2021), Genes, Volume 12, Issue 8
- 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 :
- 0301 basic medicine
Adult
Male
Globotriaosylceramide
Inflammation
Gb3
QH426-470
Article
NF-κB
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
microRNA
medicine
Genetics
Humans
Enzyme Replacement Therapy
Genetics (clinical)
Cells, Cultured
Fabry disease
biology
Trihexosylceramides
NF-kappa B
Endothelial Cells
Enzyme replacement therapy
Middle Aged
medicine.disease
In vitro
Enzyme assay
MicroRNAs
030104 developmental biology
chemistry
Gene Expression Regulation
inflammation
030220 oncology & carcinogenesis
Cancer research
biology.protein
Female
medicine.symptom
Subjects
Details
- Language :
- English
- ISSN :
- 20734425
- Volume :
- 12
- Issue :
- 1184
- Database :
- OpenAIRE
- Journal :
- Genes
- Accession number :
- edsair.doi.dedup.....a643de22e5f6c6bfcd2796429cc97dcc