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 micro mol/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.
Dhaunsi
Gursev S
GS
Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina, USA. dhaunsig@hotmail.com
Ozand
Pinar T
PT
D002478:Cells, Cultured; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology*; D004247:DNA / Q000096:biosynthesis*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D008934:Mitogens / Q000494:pharmacology*; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D012867:Skin / Q000166:cytology; D013936:Thymidine / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology
D006133:Growth Substances; D008934:Mitogens; D020030:Nitric Oxide Donors; D010982:Platelet-Derived Growth Factor; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D004247:DNA; D006152:Cyclic GMP; D013936:Thymidine