Benjamin A Juliar, Ian B Stanaway, Fumika Sano, Hongxia Fu, Kelly D Smith, Shreeram Akilesh, Suzie J Scales, Jamal El Saghir, Pavan K Bhatraju, Esther Liu, Johnson Yang, Jennie Lin, Sean Eddy, Matthias Kretzler, Ying Zheng, Jonathan Himmelfarb, Jennifer L Harder, Benjamin S Freedman
Elevated interferon (IFN) signaling is associated with kidney diseases including COVID-19, HIV, and apolipoprotein-L1 (APOL1) nephropathy, but whether IFNs directly contribute to nephrotoxicity remains unclear. Using human kidney organoids, primary endothelial cells, and patient samples, we demonstrate that IFN-γ induces pyroptotic angiopathy in combination with APOL1 expression. Single-cell RNA sequencing, immunoblotting, and quantitative fluorescence-based assays reveal that IFN-γ-mediated expression of APOL1 is accompanied by pyroptotic endothelial network degradation in organoids...
June 4, 2024: Cell Reports