Hypoxia hits APOL1 in the kidney

Grampp S, Krüger R, Lauer V, Uebel S, Knaup K, Naas J, Höffken V, Weide T, Schiffer M, Naas S, Schödel J (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Kidney International Nature Publishing Group: Open Access Hybrid Model Option A

DOI: 10.1016/j.kint.2023.03.035

Abstract

Individuals of African ancestry carrying two pathogenic variants of apolipoprotein 1 (APOL1) have a substantially increased risk for developing chronic kidney disease. The course of APOL1 nephropathy is extremely heterogeneous and shaped by systemic factors such as a response to interferon. However, additional environmental factors operating in this second-hit model have been less well defined. Here, we reveal that stabilization of hypoxia-inducible transcription factors (HIF) by hypoxia or HIF prolyl hydroxylase inhibitors activates transcription of APOL1 in podocytes and tubular cells. An active regulatory DNA-element upstream of APOL1 that interacted with HIF was identified. This enhancer was accessible preferentially in kidney cells. Importantly, upregulation of APOL1 by HIF was additive to the effects of interferon. Furthermore, HIF stimulated expression of APOL1 in tubular cells derived from the urine of an individual carrying a risk variant for kidney disease. Thus, hypoxic insults may serve as important modulators of APOL1 nephropathy.

Authors with CRIS profile

René Krüger Department of Medicine 4 – Nephrology and Hypertension Victoria Lauer Department of Medicine 4 – Nephrology and Hypertension Sebastian Uebel Department of Medicine 4 – Nephrology and Hypertension Karl Knaup Department of Medicine 4 – Nephrology and Hypertension Mario Schiffer Lehrstuhl für Innere Medizin IV Johannes Schödel Department of Medicine 4 – Nephrology and Hypertension

Involved external institutions

Universitätsklinikum Münster DE Germany (DE) Medizinische Universität Wien AT Austria (AT)

How to cite

APA:

Grampp, S., Krüger, R., Lauer, V., Uebel, S., Knaup, K., Naas, J.,... Schödel, J. (2023). Hypoxia hits APOL1 in the kidney. Kidney International. https://doi.org/10.1016/j.kint.2023.03.035

MLA:

Grampp, Steffen, et al. "Hypoxia hits APOL1 in the kidney." Kidney International (2023).

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