The Expression of DNMT1 in Pathologic Scar Fibroblasts and the Effect of 5-aza-2-Deoxycytidine on Cytokines of Pathologic Scar Fibroblasts.

OBJECTIVE

This study aimed to investigate the expression and significance of DNA methyltransferase 1 (DNMT1) in pathologic scar fibroblasts, as well as the influence of methylase inhibitor, 5-aza-2-deoxycytidine, on pathological scars.

MATERIAL AND

METHODS

Samples of 31 keloids, 20 hypertrophic scars, and 25 normal skins were taken to test the expression rate of DNMT1 by immunohistochemistry. Primary fibroblasts were cultured with the monoplast method. Samples were categorized into the keloid group (K group), 5-aza-2-deoxycytidine keloid intervention group (K+ group), normal skin group (N group), hypertrophic scar group (H group), and 5-aza-2-deoxycytidine hypertrophic scar intervention group (H+ group). The expressions of DNMT1, transforming growth factor-β (TGF-β), and Smad7 mRNA in each group were detected with realtime polymerase chain reaction. The effect of 5-aza-2-deoxycytidine on the cell cycle and apoptosis of pathologic scar fibroblasts were analyzed with flow cytometry.

RESULTS

The expression rate of DNMT1 was 100% in keloid fibroblasts, 90% in hyperplastic scar fibroblasts, and 8% in normal skin fibroblasts. After the intervention with 5-aza-2-deoxycytidine in the K+ group, the expression of DNMT1 and TGF-β1 mRNA was lower, Smad7 mRNA was elevated in pathological scar fibroblasts, the flow cytometry showed the proportion of cells in G0/G1 phase were increased, and the proportion of apoptosis cells were also increased, with similar changes in the cells in the H and H+ groups.

CONCLUSION

DNMT1 may play a vital role on the generation of pathological scars. Methylaze inhibitors 5-aza-2-deoxycytidine may influence the related cytokines of pathological scars, inhibit proliferation, and promote apoptosis of pathological scar fibroblasts. The generation of pathological scars may be related with methylation of certain genes. 5-aza-2-deoxycytidine be a new choice for the treatment of pathological scars.