Increased expression of MMP-9 is associated with poor wound healing in diabetes. NGAL binds to MMP-9 to prevent its degradation, whether NGAL coordinates with MMP-9 and its activity in diabetic wounds is not known and was examined in rodent excisional and implant wound models in this study. In this studies we have investigated neutrophil gelatinase associated lipocalin-2 (NGAL) and MMP-9, specifically focusing on the neutrophil. We used two wound models, an excisional and a implant model combined with treatment to improve blood glucose level (i.e insulin) and regulate MMP-9 (i.e doxycycline). Results show that diabetes altered neutrophil NGAL, MMP-9, and MMP-8. These changes were prevented by insulin treatment. Doxycycline treatment in particular low dose regulated some but not all of these effects. Diabetes alters circulating neutrophil NGAL in response to wounding. This may play a role in wound repair Together these results suggest that higher NGAL levels in diabetic wounds are related to higher wound fluid MMP-9 activity and that therapies targeting NGAL and MMP activities may have utility in diabetic wound healing
