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

Martijn J. Wilmer; Moin A. Saleem; Rosalinde Masereeuw; Lan Ni; Thea J. Van Der Velden; Frans G. Russel; Peter W. Mathieson; Leo A. Monnens; Lambertus P. Van Den Heuvel; Elena N. Levtchenko

doi:10.1007/s00441-009-0882-y

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

Martijn J. Wilmer
, Moin A. Saleem
, Rosalinde Masereeuw
, Lan Ni
, Thea J. Van Der Velden
, Frans G. Russel
, Peter W. Mathieson
, Leo A. Monnens
, Lambertus P. Van Den Heuvel
, Elena N. Levtchenko

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Pages (from-to)	449-457
Number of pages	9
Journal	Cell and tissue research
Volume	339
Issue number	2
DOIs	https://doi.org/10.1007/s00441-009-0882-y
Publication status	Published - Feb 2010
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Albumin endocytosis
Human
Organic cation transport
P-glycoprotein
Phosphate transport
Proximal tubule cell

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10.1007/s00441-009-0882-y

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Wilmer, M. J., Saleem, M. A., Masereeuw, R., Ni, L., Van Der Velden, T. J., Russel, F. G., Mathieson, P. W., Monnens, L. A., Van Den Heuvel, L. P., & Levtchenko, E. N. (2010). Novel conditionally immortalized human proximal tubule cell line expressing functional influx and efflux transporters. Cell and tissue research, 339(2), 449-457. https://doi.org/10.1007/s00441-009-0882-y

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title = "Novel conditionally immortalized human proximal tubule cell line expressing functional influx and efflux transporters",

abstract = "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.",

keywords = "Albumin endocytosis, Human, Organic cation transport, P-glycoprotein, Phosphate transport, Proximal tubule cell",

author = "Wilmer, \{Martijn J.\} and Saleem, \{Moin A.\} and Rosalinde Masereeuw and Lan Ni and \{Van Der Velden\}, \{Thea J.\} and Russel, \{Frans G.\} and Mathieson, \{Peter W.\} and Monnens, \{Leo A.\} and \{Van Den Heuvel\}, \{Lambertus P.\} and Levtchenko, \{Elena N.\}",

note = "Funding Information: Cystinosis Research Foundation, Cystinosis Research Network and European Community{\textquoteright}s Seventh Framework Programme (FP7/2007-2013, grant agreement n° 201590) are acknowledged for their financial support.",

year = "2010",

month = feb,

doi = "10.1007/s00441-009-0882-y",

language = "English",

volume = "339",

pages = "449--457",

journal = "Cell and tissue research",

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T1 - Novel conditionally immortalized human proximal tubule cell line expressing functional influx and efflux transporters

AU - Wilmer, Martijn J.

AU - Saleem, Moin A.

AU - Masereeuw, Rosalinde

AU - Ni, Lan

AU - Van Der Velden, Thea J.

AU - Russel, Frans G.

AU - Mathieson, Peter W.

AU - Monnens, Leo A.

AU - Van Den Heuvel, Lambertus P.

AU - Levtchenko, Elena N.

N1 - Funding Information: Cystinosis Research Foundation, Cystinosis Research Network and European Community’s Seventh Framework Programme (FP7/2007-2013, grant agreement n° 201590) are acknowledged for their financial support.

PY - 2010/2

Y1 - 2010/2

N2 - 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.

AB - 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.

KW - Albumin endocytosis

KW - Human

KW - Organic cation transport

KW - P-glycoprotein

KW - Phosphate transport

KW - Proximal tubule cell

UR - https://www.scopus.com/pages/publications/77949269535

U2 - 10.1007/s00441-009-0882-y

DO - 10.1007/s00441-009-0882-y

M3 - Article

C2 - 19902259

SN - 0302-766X

VL - 339

SP - 449

EP - 457

JO - Cell and tissue research

JF - Cell and tissue research

IS - 2

ER -

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

Abstract

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Keywords

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