Effect of lipoproteins on mesangial cell proliferation.
BACKGROUND
Triglyceride (TG)-rich lipoproteins have been reported to promote atherosclerosis, but little is known about their role in kidney disease or about their effects on mesangial cells. Accordingly, the purpose of this study was to investigate which lipoproteins could influence mesangial cell proliferation in vitro. We assessed the effect of various lipoproteins [very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low density lipoprotein (LDL), oxidized LDL, and high-density lipoprotein (HDL)] on the proliferation of cultured human mesangial cells and also assessed the influence of these lipoproteins on cytokine production.


METHODS
We investigated the effect of various lipoproteins on cultured human mesangial cells using 3H-thymidine incorporation and cell counting assays and investigated the levels of several cytokines [interleukin (IL)-6, platelet-derived growth factor (PDGF), transforming growth factor (TGF)-beta, and tumor necrosis factor-alpha] in mesangial cell culture supernatants after stimulation by the lipoproteins.


RESULTS
Not only LDL but also TG-rich lipoproteins (VLDL and IDL) promoted the proliferation of mesangial cells up to certain concentrations, but cell growth was actually decreased at higher concentrations. Oxidized LDL caused a concentration-dependent decrease of 3H-thymidine incorporation, and HDL had no proliferative effect at any concentration. Exposure to VLDL, IDL, LDL, or a high concentration of HDL enhanced the secretion of IL-6, PDGF-AB, and TGF-beta by mesangial cells, whereas TNF-alpha secretion was stimulated by oxidized LDL.


CONCLUSIONS
TG-rich lipoproteins, LDL, and oxidized LDL may be involved in mesangial cell proliferation and injury in patients with mesangial proliferative glomerulonephritis.
Nishida
Y
Y
Second Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
Oda
H
H
Yorioka
N
N
D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D008074:Lipoproteins / Q000494:pharmacology*; D008075:Lipoproteins, HDL / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008079:Lipoproteins, VLDL / Q000494:pharmacology
D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; C099252:oxidized low density lipoprotein