Analise da proliferação celular e expressão de colageno e suas proteinas chaperones, citocinas e metaloproteinas de matriz e seus inibidores teciduais em fibroblastos gengivais de pacientes com fibromatose gengival herditaria

AUTOR(ES)
DATA DE PUBLICAÇÃO

1999

RESUMO

Characterization of cellular proliferation and expression of collagen and its molecular chaperones, cytokines and matrix metalloproteinases and its tissue inhibitors in gingival fibroblasts from pacients with hereditary gingival fibromatosis Hereditary gingival fibromatosis (HGF) is a rare oral condition characterized by a slow and progressive enlargement of the gingiva, involving both the maxillaand mandible. To further elucidate some of the regulatory features resulting in this condition, the culture characteristics of the four cell lines of gingival fibroblasts derived from patients of the some family with HGF were isolated and characterized on proliferation index, collagen and its molecular chaperones production and expression, MMPs and TIMPs expression, and cytokines production. HGF and normal gingiva (NG) fibroblasts in subcofluent culture densities showed typical morphologic characteristics, but in saturation density, HGF fibroblasts were shorter than NG cells. Five different cell proliferation assays showed that the cell proliferation rate was significantly higher in HGF fibroblasts. The production and expression of Hsp47 were significantly higher in HGF fibroblasts than in NG fibroblasts, along with increased producto?n of collagen. In addition, Hsp47 is coordinately regulated by stress and by feedback mechanism mediated by N-terminal procollagen propeptides corresponding to residues of a1 (I)-chains. The cytokines production was detected by ELlSA using specific antibodies for TGF-` beta ´ 1 , IL-6, IL-1 ` beta ´ and TNF- `alfa ´. In HGF fibroblasts, the production of TGF-` beta ´ 1 and IL-6 was higher than fibroblasts from normal tissues (p<0.013 and p<0.0035 respectively), whereas IL-1` beta ´ and TNF-`alfa ´ were not detected in ali cell lines. RT-PCR and enzymographic analysis clearly demonstrated that the expression and production of MMP-1 and MMP-2 were significantly lower in fibroblasts from HGF than from NG. Interestingly, TIMP-1 and TIMP-2 expression from NG cells was shown to be slightly higher than those from HGF. The use of neutralizing antibodies to TGF-` beta ´ 1 caused a slight increase in MMP-1 and a decrease in MMP-2 expression, whereas that no change TIMPs levels. These results suggest that the pathogenesis of gingival outgrowth in HGF patients is possibly resulted of a association of factors such as increased proliferative potential, altered synthesis of collagen and Hsp47, dysregulated proteolytic balance and increased cytokines production

ASSUNTO(S)

metaloproteinas doença periodontal hereditary gingival fibromatosis matriz extracelular matrix metalloproteinases inhibitors fibroblasto colageno cellular proliferation

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