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|Type:||Artigo de periódico|
|Title:||Opposite effects of TGF-beta 1 and IFN-gamma on transdifferentiation of myofibroblast in human gingival cell cultures|
|Abstract:||Background/Aim: Previously, we have shown that myofibroblasts, the main cell type associated with interstitial fibrosis, may be implicated with the gingival overgrowth observed in hereditary gingival fibromatosis (HGF) patients. The goal of this study was to determine whether transforming growth factor-beta 1 (TGF-beta 1) stimulates myofibroblast generation in gingival fibroblast cultures. Moreover, we analysed how interferon-gamma (IFN-gamma) interferes in this process. Material and Methods: Fibroblast cultures from normal gingiva and myofibroblast cells from HGF were included in this study. To determine the effects of TGF-beta 1 and IFN-gamma stimulation in these cells, the expression of the specific myofibroblast marker smooth muscle isoform of alpha-actin (alpha-SMA) was examined by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot and immunofluorescence. Enzyme-linked immunosorbent assay (ELISA) for type I collagen was performed to measure the myofibroblast activity. Results: Our results demonstrated that TGF-beta 1 promotes a dose- and time-dependent increase in the expression of alpha-SMA, whereas IFN-gamma blocks it and markedly prevents the fibroblast-myofibroblast switch induced by TGF-beta 1 on normal gingiva cultures. IFN-gamma altered HGF myofibroblasts metabolism with a decrease of both alpha-SMA and type I collagen expression. Additionally, IFN-gamma treatment stimulated SMAD7 expression and inhibited connective tissue growth factor, which has been considered a key molecule to promote the transdifferentiation of myofibroblasts via TGF-beta 1 activation. Conclusions: These findings demonstrate that TGF-beta 1 induces gingival fibroblast-myofibroblast transdifferentiation, whereas IFN-gamma blocks this process. More importantly, this study suggests that IFN-gamma may be clinically effective in attenuating excessive accumulation of extracellular matrix produced by myofibroblasts in HGF.|
|Subject:||hereditary gingival fibromatosis|
transforming growth factor-beta 1
|Appears in Collections:||Unicamp - Artigos e Outros Documentos|
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