title: TGF-beta isoforms and TGF-beta receptors in drug-induced and hereditary gingival overgrowth.
abstract: 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 extracellular matrix production by fibroblasts. Transforming growth factor beta (TGF-beta) is an important mediator of wound healing and tissue regeneration, which stimulates fibroblasts to produce extracellular matrix materials. 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 fibromatosis (n=10) when compared to non-overgrowth tissue (n=10). Compared to control tissues, significantly more fibroblasts expressed TGF-beta1 in both DIGO and hereditary gingival fibromatosis tissues (P<0.03). Cells expressing TGF-beta2 were present at control levels in DIGO but were significantly reduced in hereditary gingival fibromatosis (P<0.02). By contrast, the number of TGF-beta3-positive cells was the same in overgrowth tissues and controls. However, because of differences in total fibroblast densities between groups, there was a proportional increase in TGF-beta3 as well as TGF-beta1 expressing cells within both overgrowth populations (P<0.0001). Furthermore, representation of the TGF-beta2-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 populations showed that the level of expression was significantly higher for TGF-beta1 in hereditary gingival fibromatosis (P<0.002) and significantly lower for TGF-beta3 in DIGO (P<0.03). No significant differences in the numbers of TGF-betaRI- or RII-positive cells were detected between overgrowth tissues and controls. However, there were increases in the proportion of receptor-positive cells in the total cell population analysed in overgrowth tissues (P<0.0001). These results indicate qualitative and quantitative differences in TGF-beta isoform and receptor expression by fibroblasts in gingival overgrowth that may contribute to disease pathogenesis.
authors.affiliation: Unit of Oral Biology & Pathology, School of Dentistry, University of Birmingham, UK.
authors.forename: H J
authors.initials: HJ
authors.lastname: Wright
authors.forename: I L
authors.initials: IL
authors.lastname: Chapple
authors.forename: J B
authors.initials: JB
authors.lastname: Matthews
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D016022:Case-Control Studies; D002452:Cell Count; D016572:Cyclosporine / Q000009:adverse effects; D005347:Fibroblasts / Q000378:metabolism; D005351:Fibromatosis, Gingival / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019214:Gingival Overgrowth / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D020033:Protein Isoforms; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis*; D018709:Statistics, Nonparametric; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
chemical_list: D020033:Protein Isoforms; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D016572:Cyclosporine