Effect of Cyclosporine A in the molecular mechanisms involved in wound healing in diabetic rats.

Abstract

The healing process is a complex phenomenon, highly specialized, where it is necessary functional integration of various types of cells, including inflammatory cells, fibroblasts, keratinocytes and endothelial cells, besides the involvement of growth factors and enzymes. Diabetes Melllitus patients are vulnerable to the development of foot ulcers resulting from multiple factors, such as neuropathy, vascular diseases and bone deformities also have a delayed healing process leading to the risk of various complications such as amputations. Recent studies show that common failures in the insulin signaling pathway in peripheral tissues and pancreatic ² cells play a central role in the development of Diabetes Mellitus. The binding of insulin to the receptor activates autophosphorylation of triggering catalyzing a phosphorylation and activation of several proteins such as AKT and mTOR. These proteins control several metabolic processes, cell proliferation and survival. The action of insulin can also be regulated by protein phosphatases which catalyze the rapid dephosphorylation of proteins involved in insulin signaling pathway. One of the most important is the PTEN, which is a negative regulator of AKT signaling and function as a tumor suppressor. Studies with cyclosporin A (drug widely used to prevent rejection of organ transplants) reveal an important function of this drug as an agent that leads to activation of AKT protein by removing the phosphatase PTEN thus resulting in the increased presence of keratinocytes in the epidermis in vitro. This project aims to evaluate the effect of topical cyclosporin A on the healing and its molecular actions on wounds of diabetic rats.