Endothelin 1, NF-κB, and ADAM-15 expression in diabetic foot wounds

The diabetic foot is an important and destructive complication of diabetes. This study examined 65 individuals (35 males, 30 females) diagnosed with diabetic foot with open wounds on their feet.

After washing the foot with isotonic solution, the wound was debrided and the excised tissues (diabetic dermis) were fixed with neutral buffered 10 % formalin solution. Specimens stained with haematoxylin-eosin, endothelin-1 (ET-1), nuclear factor kappa B (NF-κB), and ADAM 15 antibodies were used to examine angiogenesis, cytokine activity, and the extracellular matrix, respectively.

Histopathologically, in the diabetic feet of males, leukocytes, lymphocytes, and macrophages were spread diffusely throughout the lesion, with inflammatory cells invading all layers of blood vessels. In the diabetic feet of females, dilation and congestion of the blood vessels, degenerative changes in the subendothelial layer, and perivascular infiltration by lymphocytes were observed. ET-1 was expressed in inflammatory cells around pre-capillary vessels in the stromal area. NF-κB was expressed in macrophages around blood vessels, and in nodular organised cells distributed throughout the perivascular space. ADAM 15 were expressed in fibroblasts, endothelial cells, and inflammatory cells. Blood parameters differed significantly between diabetic and non-diabetic patients (Significant at p < 0.005, p < 0.001 and p < 0.0001)Conclusion: ET-1 expression in the endothelial cells of diabetic foot ulcers is an important determinant of insulin resistance at the onset of disease and induces macrophages to produce NF-κB, which regulates inflammation. It is thought that ADAM 15 contributes to angiogenic effects as a means of stimulating endothelial cells (Tab. 2, Fig. 3, Ref. 31).