Turnover of human tubular cells exposed to proteins in vivo and in vitro.
BACKGROUND
The cause of tubulointerstitial pathology in glomerular disease is uncertain. Proteinuria may be a causative factor and has been shown to increase the turnover of tubular cells in a rat model of proteinuria. We investigated whether increased tubular cell proliferation occurs in human proteinuric renal disease. A human cell culture model was used to investigate the effects of proteins on tubular cell turnover further.


METHODS
Tubular proliferation in renal biopsies from patients with membranous nephropathy (MN) and minimal change nephropathy (MCN) was assessed by in situ hybridization for histone mRNA. Proliferation was measured in polarized human tubular cell cultures using tritiated thymidine, following addition of proteins to the apical medium. Toxicity was assessed by lactate dehydrogenase (LDH) release and monolayer permeability to inulin.


RESULTS
Increased tubular cell histone mRNA expression occurred in biopsies in MN (3.0-fold increase, P < 0.002) and MCN (3.6-fold increase, P < 0.02). Serum proteins added to the medium on human tubular cell cultures increased thymidine uptake (1.3-fold, P < 0.005), LDH release (1.5-fold, P < 0.001), and monolayer permeability (1.7-fold, P < 0.005). The effects were reproduced by a fraction of molecular weight 40 to 100 kD, but not by pure albumin or transferrin.


CONCLUSIONS
Proliferation of tubular cells is associated with proteinuria in vivo and is caused by proteins in cell culture. Toxicity of proteins to tubular cells and increased cell turnover may contribute to tubulointerstitial pathology in glomerular disease.
Burton
C J
CJ
Department of Nephrology, Leicester General Hospital, Leicester, England, United Kingdom. burton_c@southmead.swest.nhs.uk
Harper
S J
SJ
Bailey
E
E
Feehally
J
J
Harris
K P
KP
Walls
J
J
D000328:Adult; D000368:Aged; D001798:Blood Proteins / Q000494:pharmacology; D002478:Cells, Cultured; D005260:Female; D015433:Glomerulonephritis, Membranous / Q000652:urine*; D006801:Humans; D007684:Kidney Tubules / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009402:Nephrosis, Lipoid / Q000652:urine*; D011507:Proteinuria / Q000209:etiology* / Q000473:pathology*
D001798:Blood Proteins; D007770:L-Lactate Dehydrogenase