Brown Adipose Tissue Improves Angiogenesis and M2 Macrophage Polarization in Burn Wounds by Activating Interleukin-17 Signaling.

Abstract

Burn wound healing is a complex physiologic process that requires complicated regulation by different cells and tissues. Brown adipose tissue (BAT) plays a key role in the hypermetabolic response to severe burns. However, it is unclear whether BAT contributes to burn wound healing. Mice were divided into 2 groups: the BAT removal group (BR group) and the control group. Burn wounds were created on the backs of mice (weighing 20 to 25 g) exposed to 100°C hot water for 12 seconds using a homemade burn tube, resulting in a burned area measuring 10 mm in diameter. The treatments were applied once a day for 10 days. Full-thickness wound tissue was collected on days 1, 4, 7, and 10, and analyzed by immunostaining of CD31, α-SMA + , F4/80, and CD206 ( n = 3). On days 4, 7, and 10, the wound-healing rate of the control group was significantly higher than that of the BR group. In the histologic analysis, evident inflammatory infiltration and severe collagen denaturation was observed in the BR group. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the interleukin-17 pathway was enriched and related genes were up-regulated in the heat map. Immunostaining and transcriptional analyses revealed that angiogenesis and fibroblasts were enhanced in the control group, and there were fewer CD206 + M2 macrophages and higher levels of inflammatory infiltration in the BR group. BAT may reduce inflammatory signaling in burn wounds by increasing the interleukin-17A-hypoxia inducible factor-1α axis and driving M2 macrophage polarization. Patients with severe burn injuries and difficult wounds are encouraged to convert white adipose tissue into beige adipose tissue using drug assistance beneath the wound. Then, browning adipose tissue could improve local angiogenesis and promote the formation of a better microenvironment for wound healing.