Effect of heparin on mesangial cell growth and gene expression of matrix proteins.

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, haemostatic, 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-beta1 (TGF-beta1) on the gene expression of those matrix proteins was assessed.

RESULTS

Within a 3-1000 microg/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 microg/ml, heparin inhibited fibronectin mRNA levels in TGF-beta1 (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.