Document Detail

The limitations of renal epithelial cell line HK-2 as a model of drug transporter expression and function in the proximal tubule.
MedLine Citation:
PMID:  23014881     Owner:  NLM     Status:  MEDLINE    
Acquiring a mechanistic understanding of the processes underlying the renal clearance of drug molecules in man has been hampered by a lack of robust in vitro models of human proximal tubules. Several human renal epithelial cell lines derived from the renal cortex are available, but few have been characterised in detail in terms of transporter expression. This includes the HK-2 proximal tubule cell line, which has been used extensively as a model of nephrotoxicity. The aim of this study was to investigate the expression and function of drug transporters in HK-2 cells and their suitability as an in vitro model of the human proximal tubule. qPCR showed no mRNA expression of the SLC22 transporter family (OAT1, OAT3, OCT2) in HK-2 cells compared to renal cortex samples. In contrast, SLC16A1 (MCT1), which is important in the uptake of monocarboxylates, and SLCO4C1 (OATP4C1) were expressed in HK-2 cells. The functional expression of these transporters was confirmed by uptake studies using radiolabelled prototypic substrates DL-lactate and digoxin, respectively. The mRNA expression of apical membrane efflux transporters ABCB1 (MDR1) and several members of the ABCC family (multidrug resistance proteins, MRPs) was shown by qPCR. ABCG1 (BCRP) was not detected. The efflux of Hoechst 33342, a substrate for MDR1, was blocked by MDR1 inhibitor cyclosporin A, suggesting the functional expression of this transporter. Similarly, the efflux of the MRP-specific fluorescent dye glutathione methylfluorescein was inhibited by the MRP inhibitor MK571. Taken together, the results of this study suggest that HK-2 cells are of limited value as an in vitro model of drug transporter expression in the human proximal tubule.
Sarah E Jenkinson; Git W Chung; Ellen van Loon; Nur S Bakar; Abigail M Dalzell; Colin D A Brown
Publication Detail:
Type:  Journal Article     Date:  2012-09-27
Journal Detail:
Title:  Pflügers Archiv : European journal of physiology     Volume:  464     ISSN:  1432-2013     ISO Abbreviation:  Pflugers Arch.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-04     Completed Date:  2013-08-19     Revised Date:  2014-05-08    
Medline Journal Info:
Nlm Unique ID:  0154720     Medline TA:  Pflugers Arch     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  601-11     Citation Subset:  IM    
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MeSH Terms
ATP-Binding Cassette Transporters / biosynthesis,  genetics,  metabolism
Biological Transport
Cell Line
Epithelial Cells / metabolism*
Kidney Cortex / cytology,  metabolism
Kidney Tubules, Proximal / cytology,  metabolism*
Membrane Transport Proteins / biosynthesis*,  genetics,  metabolism
Monocarboxylic Acid Transporters / biosynthesis,  genetics,  metabolism
Neoplasm Proteins / biosynthesis,  genetics,  metabolism
P-Glycoproteins / biosynthesis,  genetics,  metabolism
RNA, Messenger / genetics
Symporters / biosynthesis,  genetics,  metabolism
Grant Support
NC/K500240/1//National Centre for the Replacement, Refinement and Reduction of Animals in Research
Reg. No./Substance:
0/ABCG2 protein, human; 0/Membrane Transport Proteins; 0/Monocarboxylic Acid Transporters; 0/Neoplasm Proteins; 0/P-Glycoproteins; 0/RNA, Messenger; 0/Symporters; 0/monocarboxylate transport protein 1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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