Hypoxia controls expression of kidney-pathogenic MUC1 variants

Naas S, Krüger R, Knaup K, Naas J, Grampp S, Schiffer M, Wiesener M, Schödel J (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Life Science Alliance Life Science Alliance

Book Volume: 6

Article Number: e202302078

Journal Issue: 9

DOI: 10.26508/lsa.202302078

Abstract

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 59 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.

Authors with CRIS profile

Stephanie Naas Department of Medicine 4 – Nephrology and Hypertension René Krüger Department of Medicine 4 – Nephrology and Hypertension Karl Knaup Department of Medicine 4 – Nephrology and Hypertension Mario Schiffer Lehrstuhl für Innere Medizin IV Michael Wiesener Professur für Innere Medizin (Nephrologie) Johannes Schödel Department of Medicine 4 – Nephrology and Hypertension

Involved external institutions

Max Perutz Labs / Max F. Perutz Laboratories (MFPL) AT Austria (AT)

How to cite

APA:

Naas, S., Krüger, R., Knaup, K., Naas, J., Grampp, S., Schiffer, M.,... Schödel, J. (2023). Hypoxia controls expression of kidney-pathogenic MUC1 variants. Life Science Alliance, 6(9). https://doi.org/10.26508/lsa.202302078

MLA:

Naas, Stephanie, et al. "Hypoxia controls expression of kidney-pathogenic MUC1 variants." Life Science Alliance 6.9 (2023).

BibTeX: Download