The Effects of matrix metalloproteinase-14 Inhibition on diabetic Wound Healing

Abstract

Abstract Matrix metalloproteinases play critical roles in wound repair, yet their context-dependent functions in diabetic wound healing remain elusive. In this study, we found that both the expression and activity of matrix metalloproteinase-14 were significantly elevated in diabetic foot ulcers. Using animal models, we further revealed the dual roles of matrix metalloproteinase-14 in wound healing. In normal rats, inhibition of matrix metalloproteinase-14 delayed wound closure, confirming its supportive role in physiological tissue repair. In contrast, in diabetic rats, pathologically increased matrix metalloproteinase-14 levels impaired healing, whereas moderate inhibition significantly accelerated wound repair. Among the inhibitors tested, the selective matrix metalloproteinase-14 inhibitor NSC405020 produced the most favorable therapeutic effect in diabetic wounds, markedly enhancing healing rates and collagen deposition at a concentration of 1 mg/mL. Compared with the broad-spectrum matrix metalloproteinase inhibitor ND336, NSC405020 demonstrated therapeutic safety and comparable efficacy without notable toxicity in a rat model. Collectively, these findings elucidate the context-dependent role of matrix metalloproteinase-14 in wound healing, suggesting that matrix metalloproteinase-14 may be a promising therapeutic target for diabetic wound healing. Therefore, our study provides a theoretical foundation for the development of effective and safe treatments for diabetic wound management.