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

## TL;DR

This study explores how high blood sugar affects wound healing in diabetic rats by examining the expression of three key proteins involved in inflammation and blood vessel growth.

## Contribution

The study identifies how hyperglycemia modulates MAPK13, TSP1, and CXCR2 expression during wound healing in diabetic rats.

## Key findings

- Hyperglycemia increases the expression of TSP1 and CXCR2 in diabetic wound healing.
- MAPK13 expression is context-dependent under hyperglycemic conditions.
- These findings suggest potential therapeutic targets for diabetic foot ulcers.

## Abstract

Diabetes affects millions of people in the United States and can lead to serious complications, including diabetic foot ulcers (DFUs). Diabetic patients experience foot nerve damage that leads to unrecognized trauma, chronic inflammation, and reduced blood flow, resulting in nonhealing wounds and DFU formation. There are many biological pathways that contribute to wound healing and inflammation, but they are not fully understood. This study investigated three factors with critical roles in inflammation and wound healing: MAPK13, a signaling molecule for inflammation; TSP1, a protein preventing new blood vessel growth; and CXCR2, a receptor that recruits immune cells. The results revealed an increased MAPK13, TSP1, and CXCR2 with hyperglycemia. These findings suggest that hyperglycemia modulating expression of these factors contributing to chronic inflammation and decreased angiogenesis may contribute to delayed DFU healing and may be potential therapeutic targets.

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 (n = 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.