title: Restoring multidrug resistance-associated protein 3 attenuates cell proliferation in the polycystic kidney.
abstract: 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.
authors.affiliation: Department of Biological Science, Sookmyung Women's University, Seoul, Republic of Korea;
authors.forename: EunSun
authors.initials: E
authors.lastname: Chang
authors.affiliation: Department of Biological Science, Sookmyung Women's University, Seoul, Republic of Korea;
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Park
authors.affiliation: Department of Biological Science, Sookmyung Women's University, Seoul, Republic of Korea;
authors.forename: Yu mi
authors.initials: Ym
authors.lastname: Woo
authors.affiliation: Department of Nephrology in Ewha Woman's University, Seoul, Republic of Korea;
authors.forename: Duk-Hee
authors.initials: DH
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, Eulji General Hospital, Seoul, Republic of Korea; and.
authors.forename: Young-Hwan
authors.initials: YH
authors.lastname: Hwang
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Curie
authors.initials: C
authors.lastname: Ahn
authors.affiliation: Department of Biological Science, Sookmyung Women's University, Seoul, Republic of Korea; parkjh@sookmyung.ac.kr.
authors.forename: Jong Hoon
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D049109:Cell Proliferation; D004195:Disease Models, Animal; D004285:Dogs; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D061985:Madin Darby Canine Kidney Cells; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D048493:Proto-Oncogene Proteins B-raf / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D048493:Proto-Oncogene Proteins B-raf; C114462:multidrug resistance-associated protein 3; C482119:BRAF protein, human
keywords: cell proliferation; cystogenesis; multidrug resistance-associated protein 3 (MRP3); polycystic kidney