Effects of pathophysiological concentrations of albumin on NHE3 activity and cell proliferation in primary cultures of human proximal tubule cells

Am J Physiol Renal Physiol. 2003 Oct;285(4):F748-57. doi: 10.1152/ajprenal.00442.2002. Epub 2003 Jun 10.

Abstract

The progression of renal disease correlates strongly with hypertension and the degree of proteinuria, suggesting a link between excessive Na+ reabsorption and exposure of the proximal tubule to protein. The present study investigated the effects of albumin on cell growth and Na+ uptake in primary cultures of human proximal tubule cells (PTC). Albumin (1.0 mg/ml) increased cell proliferation to 134.1 +/- 11.8% (P < 0.001) of control levels with no change in levels of apoptosis. Exposure to 0.1 and 1.0 mg/ml albumin increased total 22Na+ uptake to 119.1 +/- 6.3% (P = 0.005) and 115.6 +/- 5.3% (P < 0.006) of control levels, respectively, because of an increase in Na+/H+ exchanger isoform 3 (NHE3) activity. This was associated with an increase in NHE3 mRNA to 161.1 +/- 15.1% (P < 0.005) of control levels in response to 0.1 mg/ml albumin. Using confocal microscopy with a novel antibody raised against the predicted extracellular NH2 terminus of human NHE3, we observed in nonpermeabilized cells that exposure of PTC to albumin (0.1 and 1.0 mg/ml) increased NHE3 at the cell surface to 115.4 +/- 2.7% (P < 0.0005) and 122.4 +/- 3.7% (P < 0.0001) of control levels, respectively. This effect was paralleled by significant increases in NHE3 in the subplasmalemmal region as measured in permeabilized cells. These albumin-induced increases in expression and activity of NHE3 in PTC suggest a possible mechanism for Na+ retention in response to proteinuria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins / pharmacology*
  • Apoptosis / drug effects
  • Cell Division / drug effects
  • Cells, Cultured
  • Fluorescent Antibody Technique
  • Humans
  • Kidney Tubules, Proximal / cytology*
  • Kidney Tubules, Proximal / drug effects
  • Kidney Tubules, Proximal / metabolism*
  • Kidney Tubules, Proximal / physiology
  • Microscopy, Confocal
  • Osmolar Concentration
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sodium / pharmacokinetics
  • Sodium-Hydrogen Exchanger 3
  • Sodium-Hydrogen Exchangers / genetics
  • Sodium-Hydrogen Exchangers / metabolism*

Substances

  • Albumins
  • RNA, Messenger
  • SLC9A3 protein, human
  • Sodium-Hydrogen Exchanger 3
  • Sodium-Hydrogen Exchangers
  • Sodium