Hyperglycemia Modulates the Expression of MAPK13, TSP1, and CXCR2 During Wound Healing in Sprague Dawley Rats

Diabetic foot ulcers (DFUs) are a major complication of diabetes, affecting 19-34% of diabetic patients in their lifetime. Decreased angiogenesis, altered extracellular matrix (ECM) remodeling, and chronic inflammation underlie the pathophysiology of nonhealing DFU. Further, MAPK13, which regulates matrix remodeling and promotes inflammation, CXCR2, an IL-8 receptor that drives inflammation, and thrombospondin-1 (TSP-1), which inhibits angiogenesis, play a role in wound healing, but the effect of hyperglycemia on the expression of these mediators during wound healing is not well understood. This study aims to investigate the effects of hyperglycemia on the expression of MAPK13, CXCR2, and TSP-1. Type 2 diabetes was induced in high-fat-fed Sprague Dawley rats using low-dose streptozotocin. Cutaneous wounds were created on the dorsum of control and diabetic rats. Tissue samples were collected during and after wound healing (<i>n</i> = 7 per group; total = 28) and used in this study to investigate the gene and protein expression of MAPK13, CXCR2, and TSP-1 in normal and healed skin using RT-qPCR and immunostaining. The results suggest that hyperglycemia increases the expression of TSP1 and CXCR2, and the effects on MAPK13 are context-dependent. Our results provide potential insights into impaired healing in diabetic wounds and highlight therapeutic targets for chronic DFUs by targeting angiogenesis, ECM remodeling, and chronic inflammation.