摘要：

Diabetes and its associated vascular complications e.g, cardiovascular disease and chronic wounds is a leading healthcare concern. Protein tyrosine phosphatase1B (PTP1B) is a key regulator of whole-body glucose and energy metabolism. Our recent research suggests that myeloid-specific PTP1B deletion protects against atherosclerosis. We hypothesised that inhibiting myeloid-specific (macrophage) PTP1B would improve the efficacy of wound healing that is hampered by the diabetic environment. In vivo, wound healing was assessed under physiological, normoglycemic conditions in control wildtype (PTP1Bfl/fl) and myeloid-PTP1B deficient (LysM PTP1B-/-) littermate. Experiments were conducted in streptozotocin-induced diabetic mice. Wound healing was quantified over a period of 10 days. Two circular wounds were made horizontally in the dorsal region. The wounds were assessed using tracing and ruler methods. In vitro, wound healing was assessed using wound healing assays, under hyper-glycaemic conditions. The keratinocyte cell line (HaCaT) was cultured with bone marrow-derived macrophages (BMDM) from diabetic C57Bl6 mice. Wound healing was also assessed in presence/absence of the PTP1B inhibitor, MSI-1436. Under physiological conditions, there was a significant improvement in wound healing in LysM PTP1B-/- mice 4 days- post-surgery. Under diabetic conditions, LysM PTP1B-/- mice had a significantly faster wound closure compared to PTP1Bfl/fl. on day 8 post-surgery. Wound healing assays revealed more efficient wound closure in HaCaT cells co-cultured with BMDM from diabetic C57Bl6 mice, in the presence of MSI-1436.Thus, inhibiting myeloid–PTP1B improves wound healing rate under normoglycaemic and hyperglycaemic conditions, suggesting that PTP1B inhibition as a novel therapy for treatment of non-healing wounds in diabetes and CVD.

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