TGF-beta isoforms and TGF-beta receptors in drug-induced and hereditary gingival overgrowth

Drug therapy and hereditary factors are two of the main causes of gingival overgrowth (GO). Both of these forms of GO are associated with increased ex tracellular matrix production by fibroblasts. Transforming growth factor be ta (TGF-beta) is an important mediator of wound healing and tissue regenera tion, which stimulates fibroblasts to produce extracellular matrix material s. The aim of this immunohistochemical study was to determine whether there is any altered expression of TGF-beta isoforms or its receptors in tissue from patients with drug-induced GO (DIGO; n=10) and hereditary gingival fib romatosis (n=10) when compared to non-overgrowth tissue (n=10). Compared to control tissues, significantly more fibroblasts expressed TGF-beta1 in bot h DIGO and hereditary gingival fibromatosis tissues (P<0.03). Cells express ing TGF-<beta>2 were present at control levels in DIGO but were significant ly reduced in hereditary gingival fibromatosis (P<0.02). By contrast, the n umber of TGF-<beta>3-positive cells was the same in overgrowth tissues and controls. However, because of differences in total fibroblast densities bet ween groups, there was a proportional increase in TGF-beta3 as well as TGF- beta1 expressing cells within both overgrowth populations (P<0.0001). Furth ermore, representation of the TGF-<beta>2-positive phenotype was reduced in hereditary gingival fibromatosis (P<0.01) but increased in DIGO (P<0.005) compared to controls. Absorbance measurements of the positive cell populati ons showed that the level of expression was significantly higher for TGF-be ta1 in hereditary gingival fibromatosis (P<0.002) and significantly lower f or TGF-<beta>3 in DIGO (P<0.03). No significant differences in the numbers of TGF-<beta>RI- or RII-positive cells were detected between overgrowth tis sues and controls. However, there were increases in the proportion of recep tor-positive cells in the total cell population analysed in overgrowth tiss ues (P<0.0001). These results indicate qualitative and quantitative differe nces in TGF-<beta> isoform and receptor expression by fibroblasts in gingiv al overgrowth that may contribute to disease pathogenesis.