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Hypoxia controls expression of kidney-pathogenic MUC1 variants
The interplay between genetic and environmental factors influences the course of chronic kidney disease (CKD). In this context, genetic alterations in the kidney disease gene MUC1 (Mucin1) predispose to the development of CKD. These variations comprise the polymorphism rs4072037, which alters splici...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Life Science Alliance LLC
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10267510/ https://www.ncbi.nlm.nih.gov/pubmed/37316299 http://dx.doi.org/10.26508/lsa.202302078 |
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author | Naas, Stephanie Krüger, René Knaup, Karl Xaver Naas, Julia Grampp, Steffen Schiffer, Mario Wiesener, Michael Schödel, Johannes |
author_facet | Naas, Stephanie Krüger, René Knaup, Karl Xaver Naas, Julia Grampp, Steffen Schiffer, Mario Wiesener, Michael Schödel, Johannes |
author_sort | Naas, Stephanie |
collection | PubMed |
description | The interplay between genetic and environmental factors influences the course of chronic kidney disease (CKD). In this context, genetic alterations in the kidney disease gene MUC1 (Mucin1) predispose to the development of CKD. These variations comprise the polymorphism rs4072037, which alters splicing of MUC1 mRNA, the length of a region with variable number of tandem repeats (VNTR), and rare autosomal-dominant inherited dominant-negative mutations in or 5′ to the VNTR that causes autosomal dominant tubulointerstitial kidney disease (ADTKD-MUC1). As hypoxia plays a pivotal role in states of acute and chronic kidney injury, we explored the effects of hypoxia-inducible transcription factors (HIF) on the expression of MUC1 and its pathogenic variants in isolated primary human renal tubular cells. We defined a HIF-binding DNA regulatory element in the promoter-proximal region of MUC1 from which hypoxia or treatment with HIF stabilizers, which were recently approved for an anti-anemic therapy in CKD patients, increased levels of wild-type MUC1 and the disease-associated variants. Thus, application of these compounds might exert unfavorable effects in patients carrying MUC1 risk variants. |
format | Online Article Text |
id | pubmed-10267510 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Life Science Alliance LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-102675102023-06-15 Hypoxia controls expression of kidney-pathogenic MUC1 variants Naas, Stephanie Krüger, René Knaup, Karl Xaver Naas, Julia Grampp, Steffen Schiffer, Mario Wiesener, Michael Schödel, Johannes Life Sci Alliance Research Articles The interplay between genetic and environmental factors influences the course of chronic kidney disease (CKD). In this context, genetic alterations in the kidney disease gene MUC1 (Mucin1) predispose to the development of CKD. These variations comprise the polymorphism rs4072037, which alters splicing of MUC1 mRNA, the length of a region with variable number of tandem repeats (VNTR), and rare autosomal-dominant inherited dominant-negative mutations in or 5′ to the VNTR that causes autosomal dominant tubulointerstitial kidney disease (ADTKD-MUC1). As hypoxia plays a pivotal role in states of acute and chronic kidney injury, we explored the effects of hypoxia-inducible transcription factors (HIF) on the expression of MUC1 and its pathogenic variants in isolated primary human renal tubular cells. We defined a HIF-binding DNA regulatory element in the promoter-proximal region of MUC1 from which hypoxia or treatment with HIF stabilizers, which were recently approved for an anti-anemic therapy in CKD patients, increased levels of wild-type MUC1 and the disease-associated variants. Thus, application of these compounds might exert unfavorable effects in patients carrying MUC1 risk variants. Life Science Alliance LLC 2023-06-14 /pmc/articles/PMC10267510/ /pubmed/37316299 http://dx.doi.org/10.26508/lsa.202302078 Text en © 2023 Naas et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Articles Naas, Stephanie Krüger, René Knaup, Karl Xaver Naas, Julia Grampp, Steffen Schiffer, Mario Wiesener, Michael Schödel, Johannes Hypoxia controls expression of kidney-pathogenic MUC1 variants |
title | Hypoxia controls expression of kidney-pathogenic MUC1 variants |
title_full | Hypoxia controls expression of kidney-pathogenic MUC1 variants |
title_fullStr | Hypoxia controls expression of kidney-pathogenic MUC1 variants |
title_full_unstemmed | Hypoxia controls expression of kidney-pathogenic MUC1 variants |
title_short | Hypoxia controls expression of kidney-pathogenic MUC1 variants |
title_sort | hypoxia controls expression of kidney-pathogenic muc1 variants |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10267510/ https://www.ncbi.nlm.nih.gov/pubmed/37316299 http://dx.doi.org/10.26508/lsa.202302078 |
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