Role of fibroblast Dipeptidyl peptidase 4 (DPP4/CD26) in dermal wound healing, scarring and regeneration

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Wounding of mammalian skin results in the activation of a healing program characterized by inflammation, remodeling of granulation tissue and reorganization of the extracellular matrix (ECM) which leads to the formation of a scar. On the other hand, during development, even in the presence of inflammation, skin repair proceeds without scarring until a lineage commitment of fibroblasts occurs and cells expressing DPP4 (CD26) start constituting the majority of fibroblasts in the skin. Previous investigations and own preliminary data suggest a regulatory function for DPP4 on fibroblasts. However, the exact functions of this molecule during wound healing remain unknown. Through its dipeptidase activity it might deactivate cytokines and growth factors at specific stages of wound repair and so influence the behavior of fibroblasts and other surrounding ells. Own experiments show that DPP4 is expressed and regulated on dermal cells during wound healing and when inhibited at late stages it results in increased neogenesis of hair follicles, a hallmark of regenerative repair. The present project aims to determine the pattern of expression, regulation and function of DPP4 during wound healing and wound induced hair follicle neogenesis. The knowledge generated with this investigation might identify targets for a modulation and improvement of wound healing and a reduction of scarring