Novel conditionally immortalized human proximal tubule cell line expressing functional influx and efflux transporters

被引:161
作者
Wilmer, Martijn J. [1 ]
Saleem, Moin A. [2 ]
Masereeuw, Rosalinde [3 ]
Ni, Lan [2 ]
van der Velden, Thea J. [1 ]
Russel, Frans G. [3 ]
Mathieson, Peter W. [2 ]
Monnens, Leo A. [1 ,4 ]
van den Heuvel, Lambertus P. [1 ]
Levtchenko, Elena N. [1 ,5 ]
机构
[1] Radboud Univ Nijmegen, Med Ctr, Lab Pediat & Neurol 656, NL-6500 HB Nijmegen, Netherlands
[2] Southmead Hosp, Acad Renal Unit, Bristol, Avon, England
[3] Radboud Univ Nijmegen, Med Ctr, Dept Pharmacol & Toxicol, Nijmegen Ctr Mol Life Sci, NL-6500 HB Nijmegen, Netherlands
[4] Radboud Univ Nijmegen, Dept Physiol, Med Ctr, Nijmegen Ctr Mol Life Sci, NL-6500 HB Nijmegen, Netherlands
[5] Univ Hosp Leuven, Dept Pediat, Louvain, Belgium
关键词
Proximal tubule cell; Albumin endocytosis; Phosphate transport; Organic cation transport; P-glycoprotein; Human; EPITHELIAL-CELLS; HUMAN-KIDNEY; ENDOTHELIAL-CELLS; OPOSSUM KIDNEY; PHYSIOLOGY; PHOSPHATE; CULTURE; ALBUMIN; MRP4/ABCC4; CYSTINOSIS;
D O I
10.1007/s00441-009-0882-y
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Reabsorption of filtered solutes from the glomerular filtrate and excretion of waste products and xenobiotics are the main functions of the renal proximal tubular (PT) epithelium. A human PT cell line expressing a range of functional transporters would help to augment current knowledge in renal physiology and pharmacology. We have established and characterized a conditionally immortalized PT epithelial cell line (ciPTEC) obtained by transfecting and subcloning cells exfoliated in the urine of a healthy volunteer. The PT origin of this line has been confirmed morphologically and by the expression of aminopeptidase N, zona occludens 1, aquaporin 1, dipeptidyl peptidase IV and multidrug resistance protein 4 together with alkaline phosphatase activity. ciPTEC assembles in a tight monolayer with limited diffusion of inulin-fluorescein-isothiocyanate. Concentration and time-dependent reabsorption of albumin via endocytosis has been demonstrated, together with sodium-dependent phosphate uptake. The expression and activity of apical efflux transporter p-glycoprotein and of baso-lateral influx transporter organic cation transporter 2 have been shown in ciPTEC. This established human ciPTEC expressing multiple endogenous organic ion transporters mimicking renal reabsorption and excretion represents a powerful tool for future in vitro transport studies in pharmacology and physiology.
引用
收藏
页码:449 / 457
页数:9
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