title: Involvement of DPP IV/CD26 in cutaneous wound healing process in mice.
abstract: Dipeptidyl peptidase IV (DPP IV/CD26) is a widely distributed multifunctional protein that plays a significant role in different physiological as well as pathological processes having a broad spectrum of bioactive substrates and immunomodulative properties. It has potential influence on different processes crucial for wound healing, including cell adhesion, migration, apoptosis, and extracellular matrix degradation. However, despite its known enzymatic and immunomodulative functions, limited data characterize the role of DPP IV/CD26 in cutaneous wound healing mechanisms. The aim of this study was to investigate the process of wound healing in conditions of CD26 deficiency in order to obtain better insights on the role of DPP IV/CD26 in cutaneous regeneration. Experimental wounds were made on the dorsal part of CD26 deficient (CD26-/-) and wild-type mice (C57BL/6). The process of cutaneous wound healing was monitored on defined time schedule postwounding by macroscopic, microscopic, and biochemical analyses. Obtained results revealed a better rate of wound closure, revascularization and cell proliferation in CD26-/-mice, with enhanced local expression of hypoxia-inducible factor 1α and vascular endothelial growth factor. CD26 deficiency induced prompt macrophage recruitment at the site of skin damage but did not influence mobilization of T-cells in comparison with wild-type mice. CD26-/-mice have significantly higher values of IP-10 in serum and control skins compared with wild-type mice but values in wounds did not differ significantly on days 2, 4, and 7 of wound healing. DPP IV/CD26 activity was found to be decreased 4 days postwounding in serum and 2, 4, and 7 days postwounding in wounds of wild-type animals compared with control skins. These findings contribute to better understanding of wound healing mechanisms and could give a support in finding new therapeutic approaches for wound healing and tissue regeneration.
authors.affiliation: Department of Chemistry and Biochemistry, Faculty of Medicine, University of Rijeka, Brace Branchetta 20, Rijeka, 51000, Hrvatska-Croatia.
authors.forename: Lara
authors.initials: L
authors.lastname: Baticic Pucar
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, University of Rijeka, Rijeka, Hrvatska-Croatia.
authors.forename: Ester
authors.initials: E
authors.lastname: Pernjak Pugel
authors.affiliation: Department of Chemistry and Biochemistry, Faculty of Medicine, University of Rijeka, Brace Branchetta 20, Rijeka, 51000, Hrvatska-Croatia.
authors.forename: Dijana
authors.initials: D
authors.lastname: Detel
authors.affiliation: Department of Chemistry and Biochemistry, Faculty of Medicine, University of Rijeka, Brace Branchetta 20, Rijeka, 51000, Hrvatska-Croatia.
authors.forename: Jadranka
authors.initials: J
authors.lastname: Varljen
mesh_terms: D000818:Animals; D003879:Dermatologic Agents / Q000008:administration & dosage*; D018819:Dipeptidyl Peptidase 4 / Q000008:administration & dosage* / Q000172:deficiency; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000378:metabolism; D051379:Mice; D012883:Skin Ulcer / Q000188:drug therapy* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology; D014947:Wounds and Injuries / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D003879:Dermatologic Agents; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D018819:Dipeptidyl Peptidase 4