Stromal cell-derived factor 1 (SDF-1) and its receptor CXCR4 in the formation of postburn hypertrophic scar (HTS)

Recent data support the involvement of stromal cell-derived factor 1 (SDF-1) in the homing of bone marrow-derived stem cells to wound sites during skeletal, myocardial, vascular, lung, and skin wound repair as well as some fibrotic disorders via its receptor CXCR4. In this study, the role of SDF-1/CXCR4 signaling in the formation of hypertrophic scar (HTS) following burn injury and after treatment with systemic interferon alpha 2b (IFN alpha 2b) is investigated. Studies show SDF-1/CXCR4 signaling was up-regulated in burn patients, including SDF-1 level in HTS tissue and serum as well as CD14(+)CXCR4(+) cells in the peripheral blood mononuclear cells. In vitro, dermal fibroblasts constitutively expressed SDF-1 and deep dermal fibroblasts expressed more SDF-1 than superficial fibroblasts. Lipopolysaccharide increased SDF-1 gene expression in fibroblasts. Also, recombinant SDF-1 and lipopolysaccharide stimulated fibroblast-conditioned medium up-regulated peripheral blood mononuclear cell mobility. In the burn patients with HTS who received subcutaneous IFN alpha 2b treatment, increased SDF-1/CXCR4 signaling was found prior to treatment which was down-regulated after IFN alpha 2b administration, coincident with enhanced remodeling of their HTS. Our results suggest that SDF-1/CXCR4 signaling is involved in the development of HTS by promoting migration of activated CD14(+)CXCR4(+) cells from the bloodstream to wound sites, where they may differentiate into fibrocyte and myofibroblasts and contribute to the development of HTS.