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Pharmacologic agents inhibit rat mesangial cell proliferation and collagen synthesis
1Department of Emergency Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Abstract:
Prevention of the development of end-stage renal disease is one of the most promising areas of research in nephrology. Because mesangial cell proliferation and extracellular matrix accumulation have been regarded as antecedents of glomerulosclerosis, agents that can inhibit mesangial cell proliferation may have a potential to retard the progression of renal diseases. Therefore, we investigated several clinically available agents that might affect mesangial cell proliferation and collagen synthesis in male Sprague-Dawley rats. Cell proliferation was measured by the tetrazolium dye uptake method. Collagen synthesis was measured by 3H-proline incorporation into pepsin-resistant, salt-precipitated collagen. Intracellular cAMP levels were measured by enzyme immunoassay. Our results showed that hydralazine (82% inhibition at 10 micrograms/mL), ticlopidine (61% inhibition at 30 micrograms/mL), aminophylline (66% inhibition at 200 micrograms/mL), and nicametate (91% inhibition at 1 mg/mL) inhibited serum-stimulated rat mesangial cell (RMC) growth in a dose-dependent manner. Ticlopidine (43% inhibition at 30 mg/mL), aminophylline (52% inhibition at 200 mg/mL), and nicametate (35% inhibition at 1 mg/mL) inhibited collagen synthesis in confluent RMCs. Aminophylline may act through increasing intracellular cAMP levels (9.7 +/- 0.7 pmol/mg protein at 200 micrograms/mL of aminophylline vs 4.2 +/- 0.6 pmol/mg protein at control). These data suggest that aminophylline, ticlopidine, hydralazine, and nicametate can inhibit RMC proliferation and collagen synthesis.
Insights
Several common medications, including hydralazine, ticlopidine, aminophylline, and nicametate, were found to inhibit rat mesangial cell proliferation and collagen synthesis, potentially slowing kidney disease progression.
Area of Science:
- Nephrology
- Pharmacology
Background:
- End-stage renal disease (ESRD) prevention is a key research area in nephrology.
- Mesangial cell proliferation and extracellular matrix accumulation are linked to glomerulosclerosis, a cause of kidney disease progression.
- Identifying agents that inhibit these processes could offer therapeutic potential for renal diseases.
Purpose of the Study:
- To investigate the effects of clinically available agents on rat mesangial cell (RMC) proliferation and collagen synthesis.
- To determine if these agents could be repurposed for retarding renal disease progression.
Main Methods:
- Rat mesangial cell proliferation was assessed using the tetrazolium dye uptake method.
- Collagen synthesis was quantified by measuring 3H-proline incorporation.
- Intracellular cyclic adenosine monophosphate (cAMP) levels were measured via enzyme immunoassay.
Main Results:
- Hydralazine, ticlopidine, aminophylline, and nicametate demonstrated dose-dependent inhibition of serum-stimulated RMC growth.
- Ticlopidine, aminophylline, and nicametate significantly inhibited collagen synthesis in confluent RMCs.
- Aminophylline increased intracellular cAMP levels, suggesting a potential mechanism of action.
Conclusions:
- Aminophylline, ticlopidine, hydralazine, and nicametate exhibit inhibitory effects on RMC proliferation and collagen synthesis.
- These findings suggest potential therapeutic applications for these agents in managing or slowing the progression of renal diseases.
- Further research is warranted to explore the clinical efficacy of these drugs in kidney disease prevention.