Abstract
Abstract: :
Purpose: To investigate the effect of matrix metalloproteinase (MMP) inhibition on myofibroblast–mediated matrix contraction and synthesis. Methods: Human Tenon's fibroblasts were seeded in mechanically–loaded 3D collagen gels to induce the myofibroblast phenotype. Concentrations of the broad–spectrum MMP inhibitor Ilomastat were added to the gels. Gel areas were photographed and digitally analyzed to indicate the degree of contraction. Taqman RT–PCR and ELISA were used to quantify mRNA and protein respectively for MMP–1, –2, –3 and MT1–MMP by myofibroblasts. Collagen synthesis was measured in conditioned medium of contracting gels by ELISA. Results: Ilomastat (1–100microM) significantly reduced MMP–1, –2 and –3 protein levels and collagen gel contraction (p<0.05), but MT1–MMP levels increased with the MMP inhibitor. A downregulation of MMP–1, –2 and –3 mRNA expression and an upregulation of MT1–MMP was induced with Ilomastat. Collagen production was reversibly inhibited by Ilomastat (p< 0.05). Conclusions: MMPs are produced during Tenon's myofibroblast–mediated gel contraction. Collagen production by myofibroblasts can be significantly reduced by inhibiting MMP activity. The clinical use of an MMP inhibitor may be a useful tool in limiting contractile scarring following surgery.
Keywords: wound healing • extracellular matrix