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Cell and molecular biology in hereditary gingival fibromatois Csiszar, Andrea

Abstract

Gingival overgrowth, a potential side effect of medications i.e. nifedipine, cyclosporine, is also a characteristic feature of hereditary gingival fibromatosis (HGF). Autosomal dominant, non-syndromic HGF, the most common variant, has been localized to chromosomes 2p21 -p22 (HGFI) (Hart et al., 1998; Hart et al., 2000; Hart et al., 2002; Xiao et al., 2000), 5q13-q22 (HGF2) (Xiao et al., 2001) and 2p22.3-p23.3 (HGF3) (Ye et al., 2005), suggesting genetic heterogeneity. Interestingly, one of these mutations results in constitutive activation of the signaling molecule SOS-1, which is a key regulator of cell function and gene expression. Clinical observations suggest that HGF starts at the interdental papilla area from where it expands to other areas of gingiva by a process that may resemble gingival wound healing. Since the molecular changes in HGF are largely unknown, we compared the expression of cell surface (avβ6 integrin), intracellular (SOS-1 and CK19) and extracellular matrix molecules (procollagen, FN-EDA, FN-EDB, tenascin-C, decorin, biglycan, fibromodulin, lumican) and growth factors (TGF-β and CTGF) involved in wound healing, in healthy and HGF marginal gingiva by immunohistochemical staining. We also analyzed the localization of these molecules in healthy interdental papilla. Results showed that the molecular phenotype of healthy marginal gingiva differs from that of healthy interdental papilla. Therefore, we compared the expression of target molecules in the same tissue locations (marginal gingiva) in healthy and HGF subjects. Expression of CK19 and avβ6 integrin was induced by epithelial cells in HGF samples, but they were not in healthy marginal gingiva. Furthermore, epithelial cells in HGF showed increased expression of biglycan, fibromodulin, lumican, TGF-β₁,₂,₃, CTGF and SOS-1 compared to healthy tissue. Expression of biglycan, lumican, procollagen, FN-EDB and tenascin-C were also upregulated in the extracellular matrix in HGF. Compared to healthy tissues, cell associated staining for biglycan, fibromodulin, lumican, procollagen, FN-EDB, TGF-β₁,₂,₃, and SOS-1 was increased in HGF. The latter three molecules showed also spatiotemporally increased expression in gingival experimental wounds. The repertoire of molecules that are expressed in HGF in marginal gingiva is different from healthy marginal gingiva, but shows similarities to gingival wounds and healthy interdental papilla.

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