Molecular mechanisms underlying wound healing acceleration by Staphylococcus aureus peptidoglycan

Molecular mechanisms involved in wound healing acceleration by Staphylococcus aureus peptidoglycan were investigated with the use of polyvinyl alcohol sponges implanted under the dorsal skin of rats. Total collagen and RNA content and messenger RNA levels of alpha1(I) and alpha1(III) procollagen, transforming growth factor-beta1, and matrix metalloproteinase-1 were analyzed in saline solution- and S. aureus peptidoglycan-inoculated sponges at 4, 7, 14, and 21 days after implantation. S. aureus peptidoglycan-inoculated sponges on the fourth and seventh post-operative day were surrounded and penetrated by a thick capsule of reparative connective tissue. They were considerably heavier and contained more collagen and total RNA than saline solution-inoculated sponges. Histologically, the S. aureus peptidoglycan-inoculated sponges early on contained a denser infiltrate of polymorphonuclear cells than saline solution-inoculated sponges, and later fibroblasts, macrophages, collagen, and newly formed blood vessels were more abundant in the S. aureus peptidoglycan sponges. Matrix metalloproteinase-1 messenger RNA expression was elevated at 4 days in both sponge types. However, although matrix metalloproteinase-1 mRNA levels decreased to undetectable levels by 14 days in saline solution-inoculated sponges, they remained elevated throughout the 21-day study period in S. aureus peptidoglycan-inoculated sponges. No other significant differences in the parameters analyzed were detected. These results suggest that S. aureus peptidoglycan induces an accelerated but normal wound healing process in which the markedly increased early deposition of connective tissue is rapidly remodeled likely because of a sustained expression of matrix metalloproteinase-1.