Novel mechanism for tubular injury in nephropathic cystinosis.

ABSTRACT: Understanding the unique susceptibility of the human kidney to pH dysfunction and injury in cystinosis is paramount to developing new therapies to preserve renal function. Renal proximal tubular epithelial cells (RPTECs) and fibroblasts isolated from patients with cystinosis were transcriptionally profiled. Lysosomal fractionation, immunoblotting, confocal microscopy, intracellular pH, TEM, and mitochondrial stress test were performed for validation. CRISPR, CTNS ^-/- RPTECs were generated. Alterations in cell stress, pH, autophagic turnover, and mitochondrial energetics highlighted key changes in the V-ATPases in patient-derived and CTNS^-/- RPTECs. ATP6V0A1 was significantly downregulated in cystinosis and highly co-regulated with loss of CTNS. Co

SUBMITTER: Sur S 

PROVIDER: S-EPMC11925453 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature