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 accumu lation of extracellular matrix (ECM) resulting in a generalized and fibroti c enlargement of the gingiva. To investigate some of the regulatory feature s of this condition, gingival fibroblasts from normal gingiva (NG) and HGF were examined for the expression and production of matrix metalloproteinase s (MMPs) and their inhibitors, tissue matrix metalloproteinases inhibitor ( TIMPs). Our results, obtained from 2 different assays, semi-quantitative re verse transcriptase-polymerase chain reaction (RT-PCR) and enzymography, cl early demonstrated that the expression and production of MMP-1 and MMP-2 wa s 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 facto r-beta 1 (TGF-beta 1), which is produced in greater amounts by HGF fibrobla sts, resulted in a slight increase in MMP-1 and a decrease in MMP-2 express ion, whereas TIMP-1 and TIMP-2 expressions were unaffected. These patterns of expression and production suggest that enhanced TGF-beta 1 production re duce the proteolytic activities of HGF fibroblasts, which favor the accumul ation of ECM.