Restoring multidrug resistance-associated protein 3 attenuates cell proliferation in the polycystic kidney
  • Chang, EunSun
  • Park, Eun Young
  • Woo, Yu Mi
  • Kang, Duk-Hee
  • Hwang, Young-Hwan
  • 외 2명
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초록

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.

키워드

polycystic kidneymultidrug resistance-associated protein 3 (MRP3)cell proliferationcystogenesisLONG-ACTING SOMATOSTATINAUTOSOMAL-DOMINANTLIVER-DISEASEMRP3METHOTREXATECYSTOGENESISTRANSPORTERINDUCTIONKINASEABCC2
제목
Restoring multidrug resistance-associated protein 3 attenuates cell proliferation in the polycystic kidney
저자
Chang, EunSunPark, Eun YoungWoo, Yu MiKang, Duk-HeeHwang, Young-HwanAhn, CuriePark, Jong Hoon
DOI
10.1152/ajprenal.00159.2014
발행일
2015-05
유형
Article
저널명
American Journal of Physiology - Renal Physiology
308
9
페이지
F1004 ~ F1011