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Matrix metalloproteinases in scarless wound healing Giannelis, Georgios
Objectives: Wound healing in skin often results in scar formation, whereas wound healing in oral palatal mucosa is fast and rarely results in scarring. Understanding the mechanisms that promote oral scarless wound healing may provide novel approaches to prevent scar formation in skin. The goal of the study was to compare the abundance of the major collagenases MMP-1 and MMP-13 and gelatinases MMP-2 and MMP-9 in normal unwounded oral mucosa and skin and in experimental excisional wounds in skin (healing results to scar formation) and oral mucosa (wounds heal with minimal scar formation) at various time points post-wounding at the protein level. We hypothesized that the abundance of MMPs will be higher in scarless oral mucosal wound healing, compared to skin wound healing. Methods: Experimental wounds were created in oral palatal mucosa and dorsal skin of red Duroc pigs. Wound biopsies were collected before wounding and at various time points after wounding. The abundance of MMPs at the protein level was assessed by Western blotting and zymography. Results: All studied MMPs showed a significantly increased accumulation in the wound tissue already at day three post-wounding. Their abundance remained high until day 28 when MMP-9 and MMP-13 returned to the level of unwounded tissue, while MMP-1 and MMP-2 remained significantly elevated. Oral mucosal wounds showed in general a robust early up-regulation of MMP-1, MMP-2 and MMP-9 as compared to skin wounds already at day 3 after wounding. In contrast, the peak abundance of these MMPs occurred at day 14 in skin wounds. Unwounded oral mucosa showed significantly higher abundance of total MMP-2 and active MMP-9 as compared to unwounded skin. Thus, MMPs needed for early wound healing response are already present in higher abundance in oral mucosa as compared to skin before tissue injury possibly allowing a fast wound healing response. Conclusions: Results suggest that oral mucosal wound healing is associated with fast and robust regulation of MMPs. Rapid controlled processing of wound extracellular matrix may play a key role in scarless palatal wound healing. In addition, MMPs may regulate inflammatory reaction that plays a central role in scar formation.
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