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

Abstract

Oral mucosal wounds are characterized by rapid re-epithelialization and remodelling. In vitro, oral mucosal fibroblasts exhibit a fetal phenotype with increased extracellular matrix reorganizational ability, migration and experimental wound repopulation when compared with skin fibroblasts. To investigate whether phenotypic differences in the expression and production of matrix metalloproteinase (MMP) -2 and tissue inhibitors of metalloproteinases (TIMPs) could play an important part in mediating these in vitro differences. Skin and oral mucosal fibroblast MMP-2, TIMP-1 and TIMP-2 mRNA expression and protein production were studied in three-dimensional collagen lattices using quantitative competitive reverse transcriptase-polymerase chain reaction (QCRT-PCR), enzyme-linked immunosorbent assay (ELISA), zymography and reverse zymography. Oral mucosal fibroblasts exhibited increased levels of the 62-kDa active form of MMP-2 and lattice contraction when compared with skin fibroblasts. 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 differences in TIMP activity between the skin and oral mucosal fibroblasts, as assessed by reverse zymography. These studies propose a mechanism by which fibroblast phenotype may contribute directly to the observed preferential remodelling of oral wounds.