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

Br J Dermatol. 2001 Feb;144(2):229-37. doi: 10.1046/j.1365-2133.2001.04006.x.

Abstract

Background: 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.

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: These studies propose a mechanism by which fibroblast phenotype may contribute directly to the observed preferential remodelling of oral wounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cell Culture Techniques
  • Culture Media, Conditioned
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Matrix / ultrastructure
  • Fibroblasts / enzymology*
  • Gene Expression
  • Humans
  • Male
  • Matrix Metalloproteinase 2 / biosynthesis*
  • Matrix Metalloproteinase 2 / genetics
  • Mouth Mucosa / cytology*
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin / cytology*
  • Tissue Inhibitor of Metalloproteinase-1 / biosynthesis
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tissue Inhibitor of Metalloproteinase-2 / biosynthesis
  • Tissue Inhibitor of Metalloproteinase-2 / genetics
  • Wound Healing / physiology

Substances

  • Culture Media, Conditioned
  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinase-1
  • Tissue Inhibitor of Metalloproteinase-2
  • Matrix Metalloproteinase 2