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

Cell Tissue Res. 2010 Feb;339(2):449-57. doi: 10.1007/s00441-009-0882-y. Epub 2009 Nov 10.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Alkaline Phosphatase / metabolism
  • Aquaporin 1 / metabolism
  • CD13 Antigens / metabolism
  • Cell Line, Transformed*
  • Cell Transformation, Neoplastic
  • Dipeptidyl Peptidase 4 / metabolism
  • Endocytosis / physiology
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Humans
  • Kidney Tubules, Proximal / pathology*
  • Membrane Proteins / metabolism
  • Multidrug Resistance-Associated Proteins / metabolism
  • Organic Cation Transport Proteins / metabolism*
  • Organic Cation Transporter 2
  • Phosphoproteins / metabolism
  • Zonula Occludens-1 Protein

Substances

  • ABCC4 protein, human
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Membrane Proteins
  • Multidrug Resistance-Associated Proteins
  • Organic Cation Transport Proteins
  • Organic Cation Transporter 2
  • Phosphoproteins
  • SLC22A2 protein, human
  • TJP1 protein, human
  • Zonula Occludens-1 Protein
  • Aquaporin 1
  • Alkaline Phosphatase
  • CD13 Antigens
  • Dipeptidyl Peptidase 4