title: The syndecan binding sequence KKLRIKSKEK in laminin α3 LG4 domain promotes epidermal repair.
abstract: Epithelialization of normal wounds occurs by an orderly series of events whereby keratinocytes migrate, proliferate, and differentiate to restore the barrier function. Keratinocyte migration is one of the most earliest and crucial event determining the efficiency of the overall wound repair process. Laminin 332, composed by the association of α3, β3 and γ2 chains, is a major adhesion substrate for keratinocytes and is known for its role in supporting cell adhesion and migration during wound repair. The α3 chain comprises a large globular region in its carboxyl-terminal end, which consists of five homologous globular domains (LG1-LG5), known to be involved in cellular interactions. Recent findings have suggested that the α3 chain C-terminal domains LG45 may have a role to play during the epithelialization phase in wound repair. In the present study, we have analyzed whether a peptide mimicking the major heparin binding sequence KKLRIKSKEK in α3LG45 may interact with keratinocytes to promote cell adhesion and migration. In vitro experiments supported this hypothesis and revealed that the KKLRIKSKEK peptide induces human primary keratinocyte adhesion and has the ability to promote keratinocyte migration when added in the culture medium. To examine the peptide efficacy in vivo, the KKLRIKSKEK peptide was applied over partial-thickness cutaneous wounds in pigs. Compared with vehicle-treated cutaneous wounds, the peptide application significantly promoted early-stage wound healing by accelerating re-epithelialization. Additional beneficial effects such as reduced inflammatory response and decreased granulation tissue formation were also noticed in the peptide-treated wounds.
authors.affiliation: SFR BioSciences Gerland-Lyon Sud, Institut de biologie et chimie des protéines, UMR 5305, CNRS; Université Lyon 1, 7 passage du Vercors, 69367, Lyon, France.
authors.forename: Patricia
authors.initials: P
authors.lastname: Rousselle
authors.forename: Sonia
authors.initials: S
authors.lastname: Carulli
authors.forename: Hanane
authors.initials: H
authors.lastname: Chajra
authors.forename: Guila
authors.initials: G
authors.lastname: Dayan
authors.forename: Didier
authors.initials: D
authors.lastname: Pin
authors.forename: Benjamin
authors.initials: B
authors.lastname: Herbage
keywords: cell migration; keratinocyte; laminin 332; skin; wound healing