जेनेटिक्स और जीन थेरेपी जर्नल

CC chemokine ligand-2 (CCL2) accelerates skin wound healing in diabetic mice

Toshikazu Kondo

Wound healing is a complex but well-regulated biological phenomenon and is composed of three phases such as inflammation, proliferation and maturation. In each phase of wound healing process, immune cells, mesenchymal cells and parenchymal cells play important roles through the production of biological substances, extracellular matrix and so on. Especially, chemokines can contribute to the normal wound healing process by regulating the spatiotemporal recruitment of distinct types of leukocytes. Wound healing is influenced by various kinds of systemic and local factors. Hyperglycemia is one of the major factors that have negative influence on skin wound healing. Thus, diabetic patients often show complications such as impaired skin wound repair. CCL2 is the major chemokine which recruit macrophages/monocytes. CCL2 expression is markedly enhanced at skin wound sites during the early inflammatory phase of skin wound healing process in healthy normal individuals. However, it remains elusive on the association of CCL2 with delayed skin wound healing in diabetic patients. We developed diabetic mice induced by the injection of streptozotocin (STZ). Diabetic mice demonstrated skin wound healing, with the impairment of neovascularization, CCL2 expression and macrophage infiltration, as compared with control mice. When diabetic mice were received topical CCL2 administration, delayed skin wound healing was reversed as evidenced by normalization of wound closure rates, neovascularization, collagen accumulation and infiltration of macrophages expressing vascular endothelial growth factor (VEGF), a potent angiogenic factor and transforming growth factor (TGF-β). CCL2 treatment further increased the accumulation of endothelial progenitor cell (EPC) at the wound sites of diabetic mice and eventually accelerated neovascularization. Thus, the topical application of CCL2 can be an effective therapeutic option for the treatment of diabetic patients with defective wound repair, promoting neovascularization and collagen accumulation at skin wound sites.