High-mobility group box 1 protein in human and murine skin: involvement in wound healing.
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.
Straino
Stefania
S
Laboratorio di Patologia Vascolare, Istituto Dermopatico dell'Immacolata, Istituto di Ricovero e Cura a Carattere Scientifico, Rome, Italy.
Di Carlo
Anna
A
Mangoni
Antonella
A
De Mori
Roberta
R
Guerra
Liliana
L
Maurelli
Riccardo
R
Panacchia
Laura
L
Di Giacomo
Fabio
F
Palumbo
Roberta
R
Di Campli
Cristiana
C
Uccioli
Luigi
L
Biglioli
Paolo
P
Bianchi
Marco E
ME
Capogrossi
Maurizio C
MC
Germani
Antonia
A
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
D024243:HMGB1 Protein