Hypoxia hits APOL1 in the kidney

• DOI: 10.1016/j.kint.2023.03.035
• Publication Date: 2023-04-23T13:29:21Z
• Authors: Steffen Grampp; René Krüger; Victoria Lauer; Sebastian Uebel; Karl X. Knaup; Julia Naas; Verena Höffken; Thomas Weide; Mario Schiffer; Stephanie Naas; Johannes Schödel
• Keywords: Hypoxia; Transcription

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