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Effect of the platelet-derived growth factor antagonist trapidil on mesangial cell proliferation in rats
A Futamura1, K Izumino, Y Nakagawa
12nd Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.
Abstract:
Platelet-derived growth factor (PDGF) is known as a potent mediator in the proliferation of mesangial cells in culture and in mesangial proliferative nephritis. The present study was undertaken to evaluate the effect of trapidil, an antagonist of PDGF, on mesangial cell proliferation in culture and in anti-Thy-1.1 nephritis in rats. Trapidil significantly inhibited 3H-thymidine incorporation in the mesangial cells stimulated by PDGF BB and suppressed mesangial cell proliferation in culture in a dose-dependent manner. In anti-Thy-1.1 nephritis, a significant reduction in the number of total glomerular cells and also proliferating (proliferating cell nuclear antigen positive) cells was demonstrated on day 7 in the rats treated with trapidil as compared with controls. Although renal function expressed as blood urea nitrogen and creatinine levels did not differ between rats with and without trapidil treatment, the present results suggest a salutary effect of trapidil on mesangial cell proliferation. PDGF, therefore, could play an important role in mediating mesangial cell proliferation.
Insights
Trapidil, a platelet-derived growth factor (PDGF) antagonist, effectively reduced mesangial cell proliferation in cell cultures and in a rat model of nephritis. This suggests trapidil
Area of Science:
- Nephrology
- Cell Biology
- Pharmacology
Background:
- Platelet-derived growth factor (PDGF) is a key mediator of mesangial cell proliferation.
- Mesangial cell proliferation is implicated in mesangial proliferative nephritis.
Purpose of the Study:
- To investigate the effect of trapidil, a PDGF antagonist, on mesangial cell proliferation.
- To evaluate trapidil's efficacy in an anti-Thy-1.1 nephritis rat model.
Main Methods:
- Assessed 3H-thymidine incorporation in PDGF-stimulated mesangial cells in culture.
- Administered trapidil to rats with anti-Thy-1.1 nephritis.
- Quantified glomerular cell counts and proliferating cell nuclear antigen (PCNA) positive cells.
Main Results:
- Trapidil dose-dependently inhibited PDGF-induced mesangial cell proliferation in vitro.
- Trapidil treatment significantly reduced total and proliferating glomerular cells in anti-Thy-1.1 nephritis rats.
- No significant differences in blood urea nitrogen or creatinine levels were observed between groups.
Conclusions:
- Trapidil demonstrates a beneficial effect on mesangial cell proliferation.
- PDGF plays a significant role in mediating mesangial cell proliferation in nephritis.
- Trapidil warrants further investigation for potential therapeutic applications in kidney diseases involving mesangial cell proliferation.