A tripartite complex of suPAR, APOL1 risk variants and α_vβ₃ integrin on podocytes mediates chronic kidney disease.

ABSTRACT: Soluble urokinase plasminogen activator receptor (suPAR) independently predicts chronic kidney disease (CKD) incidence and progression. Apolipoprotein L1 (APOL1) gene variants G1 and G2, but not the reference allele (G0), are associated with an increased risk of CKD in individuals of recent African ancestry. Here we show in two large, unrelated cohorts that decline in kidney function associated with APOL1 risk variants was dependent on plasma suPAR levels: APOL1-related risk was attenuated in patients with lower suPAR, and strengthened in those with higher suPAR levels. Mechanistically, surface plasmon resonance studies identified high-affinity interactions between suPAR, APOL1 and α_vβ₃ integrin, whereby APOL1 protein variants G1 and G2 exhibited higher affinity for s

SUBMITTER: Hayek SS 

PROVIDER: S-EPMC6019326 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature