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Antithrombin III inhibits mesangial cell proliferation
M V Pahl1, N D Vaziri, F Oveisi
1Department of Medicine, University of California, Irvine Medical Center 92668, USA.
Journal of the American Society of Nephrology : JASN
|October 1, 1996
Summary
Antithrombin III effectively inhibits thrombin-stimulated mesangial cell proliferation, similar to heparin. This suggests antithrombin III is a key regulator of thrombin's mitogenic effects, independent of heparin.
Area of Science:
- Nephrology
- Cell Biology
- Biochemistry
Background:
- Thrombin stimulates mesangial cell proliferation, while heparin and heparan sulfate inhibit it.
- Heparin's anticoagulant effects are mediated by antithrombin III.
- The role of antithrombin III in heparin's antiproliferative action was unclear.
Purpose of the Study:
- To investigate if antithrombin III mediates heparin's antiproliferative effects on mesangial cells.
- To determine the effect of antithrombin III on thrombin-stimulated mesangial cell growth.
Main Methods:
- Cultured human mesangial cells were used.
- Thrombin was employed to stimulate DNA synthesis and cell growth.
- The effects of heparin and antithrombin III, alone and in combination, were assessed.
- Experiments were conducted in serum-free medium to evaluate antithrombin III independence.
Main Results:
- Thrombin significantly stimulated mesangial cell DNA synthesis and proliferation.
- Both standard heparin and antithrombin III inhibited thrombin-induced proliferation.
- Antithrombin III's inhibitory effect was comparable to equimolar heparin.
- Heparin's inhibitory effects were observed to be independent of antithrombin III in serum-free conditions.
Conclusions:
- Antithrombin III is an effective inhibitor of thrombin's mitogenic action on mesangial cells.
- This inhibitory action is comparable in magnitude to that of heparin.
- Heparin's antiproliferative effects are independent of antithrombin III.