Study on the mechanism of collagen metabolism in phenytoin-induced gingival overgrowth

Gingival overgrowth is a serious adverse effect associated with the administration of phenytoin (PHT), with PHT-induced gingival overgrowth characterized by a massive accumulation of extracellular matrix components, especially collagen, in gingival connective tissues. However, the etiology of such collagen accumulation is still largely unknown. We examined the effects of PHT on the collagen degradation process leading to collagen accumulation in human gingival fibroblasts (HGF). PHT causes an impaired degradation of collagen by suppression of enzymatic degradation with MMPs/TIMP-1 and ƒ¿2 ƒÀ1 integrin mediated endocytosis. These synergistic effects may cause collagen accumulation, leading to gingival overgrowth. It has also been reported that dental plaque is the most important factor to enhance deterioration caused by PHT-induced