Nitric oxide promotes mitogen-induced DNA synthesis in human dermal fibroblasts through cGMP

1. Nitric oxide (NO) is a free radical with multiple functions in cellular pathophysiology. Nitric oxide has been proven to play an important role in wound healing; however, the mechanisms by which NO may promote wound healing are not clearly understood. We have investigated the effect of NO on growth factor-induced DNA synthesis in human dermal fibroblasts to suggest interactions between growth factors and NO as a possible mechanism for the role of NO in wound healing. 2. The NO donor sodium nitroprusside (SNP) significantly (P < 0.001) increased fetal bovine serum-induced thymidine incorporation into the DNA of human dermal fibroblasts. The maximal comitogenic concentration of SNP (100 mumol/L) was also found to significantly (twofold; P < 0.01) enhance fibroblast growth factor- or platelet-derived growth factor-induced DNA synthesis. 3. Nitric oxide treatment significantly increased the production of cGMP. 8-Bromo-cGMP, a stable structural analogue of cGMP, was found to markedly potentiate (P < 0.001) the growth factor-induced DNA synthesis. 4. This study concludes that NO and cGMP promote growth factor-induced DNA synthesis in dermal fibroblasts, suggesting another possible mechanism by which NO may promote skin wound healing.