Dataset Information

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

ABSTRACT: 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. 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. 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. We suggest that let-7a and let-7d are potential markers for enzyme activity and inflammation in Fabry disease patients.

SUBMITTER: Maier N

PROVIDER: S-EPMC8394417 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Publications

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

Maier Nadine N Gatterer Constantin C Haider Patrick P Salzmann Manuel M Kaun Christoph C Speidl Walter S WS Sunder-Plassmann Gere G Podesser Bruno K BK Wojta Johann J Graf Senta S Lenz Max M Hohensinner Philipp J PJ

Genes 20210730 8

<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>In a micro-RN ...[more]

PMID: 34440358

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Dataset Information

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

Publications

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

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