Alteration in expression of MMP-1 and MMP-2 but not TIMP-1 and TIMP-2 in hereditary gingival fibromatosis is mediated by TGF-beta 1 autocrine stimulation.
Hereditary gingival fibromatosis (HGF) is characterized by an excess accumulation of extracellular matrix (ECM) resulting in a generalized and fibrotic enlargement of the gingiva. To investigate some of the regulatory features of this condition, gingival fibroblasts from normal gingiva (NG) and HGF were examined for the expression and production of matrix metalloproteinases (MMPs) and their inhibitors, tissue matrix metalloproteinases inhibitor (TIMPs). Our results, obtained from 2 different assays, semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and enzymography, clearly demonstrated that the expression and production of MMP-1 and MMP-2 was 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 to those from HGF. Addition of antibodies against transforming growth factor-beta 1 (TGF-beta 1), which is produced in greater amounts by HGF fibroblasts, resulted in a slight increase in MMP-1 and a decrease in MMP-2 expression, whereas TIMP-1 and TIMP-2 expressions were unaffected. These patterns of expression and production suggest that enhanced TGF-beta 1 production reduce the proteolytic activities of HGF fibroblasts, which favor the accumulation of ECM.
Coletta
R D
RD
Department of Oral Pathology, Dental School, University of Campinas Piracicaba, São Paulo, Brazil. coletta@fop.unicamp.br
Almeida
O P
OP
Reynolds
M A
MA
Sauk
J J
JJ
D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D005347:Fibroblasts / Q000201:enzymology; D005351:Fibromatosis, Gingival / Q000201:enzymology / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D005881:Gingiva / Q000166:cytology / Q000201:enzymology; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000096:biosynthesis*
D017931:DNA Primers; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1