title: Fibronectin production by human tubular cells: the effect of apical protein.
abstract: In progressive renal disease the degree of renal failure correlates with interstitial scarring and the rate of progression correlates with the degree of proteinuria. This has led to the hypothesis that proteinuria may cause interstitial scarring. Human tubular cells (HTC) grown on permeable membrane supports were characterized to be predominantly of proximal tubular origin. HTC produce the matrix protein fibronectin in a polarised fashion the ratio of basolateral to apical secretion being 2.9 +/- 0.2 at 48 hours. The addition of serum proteins (1.0 mg/ml) to the apical medium resulted in increased basolateral secretion of fibronectin, 2.62 +/- 0.23-fold after 24 hours and 2.40 +/- 0.16-fold after 48 hours. Serum fractionation revealed that the stimulant to fibronectin production had a molecular weight 40 to 100 kDa. Platelet derived growth factor secretion was also stimulated to apical exposure to serum but transforming growth factor beta secretion was not detected. Addition of neutralizing anti-PDGF antibodies did not decrease fibronectin secretion. The activity of serum was not reproduced by albumin or by transferrin. Exposure of HTC to serum resulted in increased release of lactate dehydrogenase, suggesting a degree of cytotoxicity. This evidence could provide a mechanism for the link between proteinuria and interstitial scarring.
authors.affiliation: Department of Nephrology, Leicester General Hospital, England, United Kingdom.
authors.forename: C J
authors.initials: CJ
authors.lastname: Burton
authors.forename: C
authors.initials: C
authors.lastname: Combe
authors.forename: J
authors.initials: J
authors.lastname: Walls
authors.forename: K P
authors.initials: KP
authors.lastname: Harris
mesh_terms: D000418:Albumins / Q000493:pharmacokinetics / Q000494:pharmacology; D000906:Antibodies / Q000494:pharmacology; D000954:Antigens, Surface / Q000096:biosynthesis; D001798:Blood Proteins / Q000494:pharmacology; D002458:Cell Fractionation; D002463:Cell Membrane Permeability / Q000502:physiology; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D003603:Cytotoxins / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000096:biosynthesis*; D006358:Hot Temperature; D006801:Humans; D007457:Iodine Radioisotopes; D007684:Kidney Tubules / Q000166:cytology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008970:Molecular Weight; D009500:Neutralization Tests; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000276:immunology; D014168:Transferrin / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
chemical_list: D000418:Albumins; D000906:Antibodies; D000954:Antigens, Surface; D001798:Blood Proteins; D003603:Cytotoxins; D005353:Fibronectins; D007457:Iodine Radioisotopes; D010982:Platelet-Derived Growth Factor; D014168:Transferrin; D016212:Transforming Growth Factor beta; D007770:L-Lactate Dehydrogenase