MiRNA Let-7a and Let-7d Are Induced by Globotriaosylceramide via NF-kB Activation in Fabry Disease

Genes (Basel) 2021 Jul 30;12(8):1184. doi: 10.3390/genes12081184.

PMID: 34440358

Nadine Maier, Constantin Gatterer, Patrick Haider

Highlights: According to the findings of this study, Let-7a and Let-7d may be useful indicators for enzyme activity and inflammation in Fabry disease patients.

Abstract

Background: Fabry disease is caused by a hereditary genetic abnormality that causes a decrease in the enzyme α-galactosidase-A activity and the accumulation of globotriaosylceramide (Gb3) in bodily fluids and cells. The vascular endothelium in various organs has been found to accumulate Gb3.

Methods: A micro-RNA screen was used to screen three Fabry disease patients. Gb3 regulation of miRNA was studied in human endothelial cells using an in vitro approach.

Results: In a micro-RNA screen of three Fabry patients, we discovered that miRNAs Let-7a and Let-7d were considerably elevated following enzyme replacement treatment. Gb3 stimulated NF-κB activation and activated downstream targets in endothelial cells were demonstrated in vitro, according to our findings. Furthermore, blocking NF-κB nuclear entry eliminated the Gb3 effects, since NF-κB activity directly lowered Let-7a and Let-7d miRNA expression.

Conclusion: Let-7a and Let-7d may be useful indicators for enzyme activity and inflammation in Fabry disease patients, according to our findings.

Keywords: Fabry, Gb3, NF-κB, inflammation