Autosomal dominant polycystic kidney disease (ADPKD) is characterized by abnormal proliferation of renal tubular epithelial cells resulting in loss of renal function. Despite identification of the genes responsible for ADPKD, few effective drugs are currently available for the disease. Thus, finding additional effective drug targets is necessary. The functions of MRP3 have been reported only in the field of drug-resistance, and the renal functions of multidrug-resistance associated protein 3 (MRP) are mostly unknown. In this study, we found that MRP3 was significantly downregulated in kidneys of human patients with ADPKD and polycystic kidney disease (PKD) mouse models. Our results suggest that downregulated MRP3 stimulated renal epithelial cell proliferation through the B-Raf/MEK/ERK signaling pathway. In contrast, we found that restoring MRP3 reduced cell proliferation and cystogenesis in vitro. These results suggest that the renal function of MRP3 is related to renal cell proliferation and cyst formation and that restoring MRP3 may be an effective therapeutic approach for PKD.
- Polycystic kidney
- Multidrug resistance-associated protein 3 (MRP3)
- Cell proliferation
- Copyright © 2014, American Journal of Physiology - Renal Physiology