Nephrology Dialysis Transplantation, Vol 13, Issue 12 3052-3057, Copyright © 1998 by Oxford University Press
Z Wang, K Liang, M Pahl and N Vaziri
Background. Mesangial cell (MC) proliferation and
matrix expansion are characteristics of many glomerulopathies. Heparin has
been shown to inhibit MC proliferation in vitro and
mitigate cell proliferation, matrix expansion, proteinuria, renal
insufficiency, and hypertension in experimental glomerulonephritis and
subtotal renal ablation. We examined the effect of standard heparin on MC
proliferation and matrix protein expression in vitro
which necessarily excludes the confounding influences of haemodynamic,
inflammatory, heamostatic, and various other processes that are present
in vivo. Methods. Gene expression
and release of fibronectin (FN), collagen IV and laminin by cultured rat MC
were tested in the presence and absence of heparin. In addition the effect
of transforming growth factor-{beta}1 (TGF-{beta}1) on the gene
expression of those matrix proteins was assessed. Results.
Within a 3-1000 &mgr;g/ml concentration range, heparin
inhibited gene expression and release of FN by 10% fetal calf serum
(FCS)-stimulated MC in a concentration-dependent manner. At concentrations
of 300 and 1000 &mgr;g/ml, heparin inhibited fibronectin mRNA levels in
TGF-{beta}1 (6 ng/ml) stimulated cells. However, heparin had no effect
on gene expression or release of collagen IV or laminin under these
conditions. Heparin markedly inhibited 10% FCS-stimulated MC proliferation
in a concentration-dependent manner. Conclusions.
Heparin inhibited MC growth and fibronectin production. These
effects may, in part, account for the reported beneficial effects of
heparin on the course of renal disease in experimental animals.
Keywords: collagen, laminin, fibronectin,
TGF-{beta}1
ORIGINAL ARTICLES
Effect of heparin on mesangial cell growth and gene expression of matrix proteins
Division of Nephrology, Department of Medicine, University of California, Irvine, CA, USA; Corresponding author address: Division of Nephrology, UCI Medical Centre, 101 The City Drive, Orange, CA 92868, USA
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