The effect of epidermal growth factor on matrix metalloproteinases and tissue inhibitors of metalloproteinase gene expression in cultured human gingival fibroblasts

Objective: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (Timps) play a role in the breakdown of the extracellular matrix during normal physiological processes, and in pathological processes, including periodontitis. The aim of this study was to evaluate the effect of epidermal growth factor (EGF) on the expression of MMPs and TIMPs in cultured human gingival fibroblasts. Methods: Fibroblasts were stimulated with 10-3, 10(-6) or 10(-12) M EGF for 24 h; untreated fibroblasts served as controls. Alterations in the expression of MMP-1, 2, 3, 7, 11, TIMP-1 and 2 were evaluated using real-time PCR and Western blotting. P-Actin expression was used as a reference to normalize gene expression. Results: Increased MMP-1, 3, 7 and 11 expressions were observed at all EGF concentrations (p < 0.05). At the lowest EGF concentration, MMP-1, 3 and 7 presented the lowest expression and MMP-11 presented the greatest expression; at higher EGF concentrations, MMP-1, 3 and 7 presented greater up-regulation, and MMP-11 lower up-regulation (p < 0.05). Protein expression was similarly regulated by EGF: increased up-regulation of MMP-1, 3 and 7 was observed with increasing EGF concentrations, except for MMP-11 that exhibited greater up-regulation at the lower EGF concentration. The gene expression of MMP-2, TIMP-1 and 2 was not affected by EGF (p < 0.05). Conclusions: We conclude that EGF regulates expression for MMP-1, 3, 7 and 11 in a dose-dependent manner, suggesting that EGF may play a role in periodontal destruction and wound repair. (C) 2006 Published by Elsevier Ltd.