PFOS increases cellular uric acid content and the abundance of URAT1 and GLUT9 in HK-2 cells

Perfluorooctane sulfonate (PFOS) is a persistent environmental pollutant associated with hyperuricemia. How PFOS affects urate-related responses in human proximal-tubule cells remains incompletely understood. We examined cellular uric acid content and URAT1/GLUT9 protein abundance in PFOS-treated HK-2 cells, with benzbromarone as a pharmacological comparator. Network analysis, molecular docking, molecular dynamics simulations and public mouse kidney single-cell RNA sequencing provided complementary candidate and cell-type information. PFOS increased cellular uric acid content under exogenous-urate conditions and increased URAT1/GLUT9 abundance; combined PFOS and benzbromarone treatment attenuated these responses. Cell Counting Kit-8 (CCK-8) profiles showed greater signal reductions at 48 h than at 24 h. Intersection analysis identified 49 PFOS-hyperuricemia candidate genes, with enrichment of transport-related functions and peroxisome proliferator-activated receptor signalling. Docking and one 100-ns trajectory per complex described predicted PFOS interactions with URAT1 and GLUT9. Candidate-gene signature scores were highest in proximal convoluted tubule cells in a public Uox-knockout hyperuricemia dataset without PFOS exposure. Together, these findings identify a PFOS-associated cellular phenotype involving uric acid accumulation and altered transporter abundance. The respective contributions of URAT1 and GLUT9 to transport function, and the relevance of these responses in vivo, remain questions for direct functional studies.