Expression and activity of matrix metalloproteinase‐2 and ‐9 in experimental granulation tissue

Abstract

The restoration of functional connective tissue is a major goal of the wound healing process which is probably affected by matrix-modifying enzymes. To evaluate the spatial and temporal expression of matrix metalloproteinases (MMP) MMP-2 and MMP-9 and to study the regulation of MMP-2 in wound healing, subcutaneously implanted viscose cellulose sponges in rats were used to induce granulation tissue formation for up to 3 months. MMP-2 mRNA expression was seen throughout the experiment and it was highest after 2 months. MMP-9 gene expression was low between days 8-21 and increased after 4 weeks of granulation tissue formation. Membrane-type 1 MMP (MT1-MMP) mRNA was upregulated early and tissue inhibitor 2 of MMP (TIMP-2) mRNA later during wound healing. In in situ hybridization the expression of MMP-2 mRNA was seen mostly in fibroblast-like cells and MMP-9 mRNA in macrophage-like cells. MMP-9 immunoreactivity was detected in the polymorphonuclear leukocytes and macrophage-like cells on days 3-8. MMP-9 proteolytic activity was observed only on days 3-8. The active form of the MMP-2 increased up to day 14, whereafter it remained at a constant level, whereas latent MMP-2 did not show any apparent changes during the experimental period. We conclude that MMP-2 is important during the prolonged remodelling phase, whereas the gelatinolytic activity of MMP-9 was demonstrated only in early wound healing, and the MMP-9 gene is upregulated when the granulation tissue matures.

Hypoxia and Upregulation of Hypoxia-Inducible Factor 1α Stimulate Venous Thrombus Recanalization

“…10 MMP9 has been found in abundance in the resolving thrombus 63 and could facilitate thrombus canalization by degrading its extracellular matrix to facilitate the migration of endothelial cells. 70 Net extracellular matrix turnover is also affected by the level of the MMP inhibitor TIMP1. 71 The higher levels of TIMP seen in this study may reflect the increased production of MMP9, as this inhibitor is expressed to prevent MMP overactivity under physiological conditions.…”

Tracking Healing Process of Experimental Liver Injuries Treated with Different Sealants and Adhesives Biomaterials. Matrix Metalloproteinase Evaluation

“…[26] Gelatinases (MMP2 and MMP9) play an important role in the formation and maturation of granulation tissue during wound healing. [27] Both MMP2 and MMP9 have been reported to act synergistically with collagenases. [28] Once collagenases have cleaved the collagen triple helix, gelatinases begin degrading the Type I, II and III collagen fibers.…”

In vivowound-healing efficacy and antioxidant activity ofAchyranthes asperain experimental burns

“…Matrix metalloproteinases (MMPs) are key players in every phase of the healing process, that is, eliminate damaged protein, destroy provisional extracellular matrix, facilitate migration to the centre of the wound, remodel the granulation tissue, probably control angiogenesis and also regulate the activity of some growth factors (Inkinen et al, 2000). Increased expression of MMP-2 and 9 in 18.5 ± 1.2 17.9 ± 0.9 17.5 ± 1.0 WBC (×10 3 cells/μL) 12.8 ± 0.8 13.0 ± 0.8 15.7 ± 0.9 RBC (×10 6 cells/μL) 8.4 ± 0.9 9.4 ± 0.9 8.4 ± 0.6 SGPT (IU/L) 51.0 ± 1.3 50.1 ± 1.9 51.0 ± 1.3 SGOT (IU/L) 87.1 ± 2.3 87.8 ± 2.4 84.7 ± 1.9 Total protein (g/dL)…”