Restoring multidrug resistance-associated protein 3 attenuates cell proliferation in the polycystic kidney
- 주제(키워드) polycystic kidney , multidrug resistance-associated protein 3 (MRP3) , cell proliferation , cystogenesis
- 등재 SCIE, SCOPUS
- 발행기관 AMER PHYSIOLOGICAL SOC
- 발행년도 2015
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000115603
- 본문언어 영어
- Published As http://dx.doi.org/10.1152/ajprenal.00159.2014
초록/요약
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by abnormal proliferation of renal tubular epithelial cells, resulting in the 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 multidrug-resistance-associated protein 3 (MRP3) have been reported only in the field of drug resistance, and the renal functions of MRP3 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.
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