title: High-mobility group box 1 protein in human and murine skin: involvement in wound healing.
abstract: High-mobility group box 1 (HMGB1) protein is a multifunctional cytokine involved in inflammatory responses and tissue repair. In this study, it was examined whether HMGB1 plays a role in skin wound repair both in normoglycemic and diabetic mice. HMGB1 was detected in the nucleus of skin cells, and accumulated in the cytoplasm of epidermal cells in the wounded skin. Diabetic human and mouse skin showed more reduced HMGB1 levels than their normoglycemic counterparts. Topical application of HMGB1 to the wounds of diabetic mice enhanced arteriole density, granulation tissue deposition, and accelerated wound healing. In contrast, HMGB1 had no effect in normoglycemic mouse skin wounds, where endogenous HMGB1 levels may be adequate for optimal wound closure. Accordingly, inhibition of endogenous HMGB1 impaired wound healing in normal mice but had no effect in diabetic mice. Finally, HMGB1 had a chemotactic effect on skin fibroblasts and keratinoyctes in vitro. In conclusion, lower HMGB1 levels in diabetic skin may play an important role in impaired wound healing and this defect may be overcome by the topical application of HMGB1.
authors.affiliation: Laboratorio di Patologia Vascolare, Istituto Dermopatico dell'Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Straino
authors.forename: Anna
authors.initials: A
authors.lastname: Di Carlo
authors.forename: Antonella
authors.initials: A
authors.lastname: Mangoni
authors.forename: Roberta
authors.initials: R
authors.lastname: De Mori
authors.forename: Liliana
authors.initials: L
authors.lastname: Guerra
authors.forename: Riccardo
authors.initials: R
authors.lastname: Maurelli
authors.forename: Laura
authors.initials: L
authors.lastname: Panacchia
authors.forename: Fabio
authors.initials: F
authors.lastname: Di Giacomo
authors.forename: Roberta
authors.initials: R
authors.lastname: Palumbo
authors.forename: Cristiana
authors.initials: C
authors.lastname: Di Campli
authors.forename: Luigi
authors.initials: L
authors.lastname: Uccioli
authors.forename: Paolo
authors.initials: P
authors.lastname: Biglioli
authors.forename: Marco E
authors.initials: ME
authors.lastname: Bianchi
authors.forename: Maurizio C
authors.initials: MC
authors.lastname: Capogrossi
authors.forename: Antonia
authors.initials: A
authors.lastname: Germani
mesh_terms: D000818:Animals; D002633:Chemotaxis; D003593:Cytoplasm / Q000378:metabolism; D048909:Diabetes Complications / Q000378:metabolism / Q000628:therapy; D000078404:Epidermal Cells; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D024243:HMGB1 Protein / Q000096:biosynthesis* / Q000502:physiology*; D006801:Humans; D007249:Inflammation; D015603:Keratinocytes / Q000166:cytology; D051379:Mice; D008954:Models, Biological; D012867:Skin / Q000473:pathology; D014945:Wound Healing
chemical_list: D024243:HMGB1 Protein