Skin and oral fibroblasts exhibit phenotypic differences in extracellular matrix reorganization and matrix metalloproteinase activity

Background Oral mucosal wounds are characterized by rapid re-epithelializat ion and remodelling. In vitro, oral mucosal fibroblasts exhibit a fetal phe notype with increased extracellular matrix reorganizational ability migrati on and experimental wound repopulation when compared with skin fibroblasts. Objectives To investigate whether phenotypic differences in the expression and production of matrix metalloproteinase (MMP) -2 and tissue inhibitors o f metalloproteinases (TIMPs) could play an important part in mediating thes e in vitro differences, Methods Skin and oral mucosal fibroblast MMP-2, TIMP-1 and TIMP-2 mRNA expr ession and protein production were studied in three-dimensional collagen la ttices using quantitative competitive reverse transcriptase-polymerase chai n reaction (QCRT-PCR), enzyme-linked immunosorbent assay (ELISA), zymograph y and reverse zymography. Results Oral mucosal fibroblasts exhibited increased levels of the 62-kDa a ctive form of MMP-2 and lattice contraction when compared with skin fibrobl asts. Oral mucosal and skin fibroblast MMP-2 gene expression and synthesis of the 72-kDa pro-MMP-2 was similar as assessed by QCRT-PCR, zymography and ELISA, Differential MMP-2 activation was, however, related to phenotypic d ifferences in TIMP activity between the skin and oral mucosal fibroblasts, as assessed by reverse zymography, Conclusions These studies propose a mechanism by which fibroblast phenotype may contribute directly to the observed preferential remodelling of oral w ounds.