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MiRNA Let-7a and Let-7d Are Induced by Globotriaosylceramide via NF-kB Activation in Fabry Disease
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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394417/ https://www.ncbi.nlm.nih.gov/pubmed/34440358 http://dx.doi.org/10.3390/genes12081184 |
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author | Maier, Nadine Gatterer, Constantin Haider, Patrick Salzmann, Manuel Kaun, Christoph Speidl, Walter S. Sunder-Plassmann, Gere Podesser, Bruno K. Wojta, Johann Graf, Senta Lenz, Max Hohensinner, Philipp J. |
author_facet | Maier, Nadine Gatterer, Constantin Haider, Patrick Salzmann, Manuel Kaun, Christoph Speidl, Walter S. Sunder-Plassmann, Gere Podesser, Bruno K. Wojta, Johann Graf, Senta Lenz, Max Hohensinner, Philipp J. |
author_sort | Maier, Nadine |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8394417 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83944172021-08-28 MiRNA Let-7a and Let-7d Are Induced by Globotriaosylceramide via NF-kB Activation in Fabry Disease Maier, Nadine Gatterer, Constantin Haider, Patrick Salzmann, Manuel Kaun, Christoph Speidl, Walter S. Sunder-Plassmann, Gere Podesser, Bruno K. Wojta, Johann Graf, Senta Lenz, Max Hohensinner, Philipp J. Genes (Basel) Article 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. MDPI 2021-07-30 /pmc/articles/PMC8394417/ /pubmed/34440358 http://dx.doi.org/10.3390/genes12081184 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Maier, Nadine Gatterer, Constantin Haider, Patrick Salzmann, Manuel Kaun, Christoph Speidl, Walter S. Sunder-Plassmann, Gere Podesser, Bruno K. Wojta, Johann Graf, Senta Lenz, Max Hohensinner, Philipp J. MiRNA Let-7a and Let-7d Are Induced by Globotriaosylceramide via NF-kB Activation in Fabry Disease |
title | MiRNA Let-7a and Let-7d Are Induced by Globotriaosylceramide via NF-kB Activation in Fabry Disease |
title_full | MiRNA Let-7a and Let-7d Are Induced by Globotriaosylceramide via NF-kB Activation in Fabry Disease |
title_fullStr | MiRNA Let-7a and Let-7d Are Induced by Globotriaosylceramide via NF-kB Activation in Fabry Disease |
title_full_unstemmed | MiRNA Let-7a and Let-7d Are Induced by Globotriaosylceramide via NF-kB Activation in Fabry Disease |
title_short | MiRNA Let-7a and Let-7d Are Induced by Globotriaosylceramide via NF-kB Activation in Fabry Disease |
title_sort | mirna let-7a and let-7d are induced by globotriaosylceramide via nf-kb activation in fabry disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394417/ https://www.ncbi.nlm.nih.gov/pubmed/34440358 http://dx.doi.org/10.3390/genes12081184 |
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