Role of the elastin receptor complex (S-Gal/Cath-A/Neu-1) in skin repair and regeneration.
Impaired elastic fiber assembly constitutes one major problem in skin wound healing. Recent data indicate that a ternary complex involving a splicing form of beta-galactosidase associated with cathepsin-A and neuraminidase-1 directs the transport of tropoelastin to the fibroblast plasma membrane and participates in the deposition of the elastin precursor onto a microfibrillar scaffold. In addition, this elastin receptor complex is ubiquitously expressed and also acts as a true receptor for elastin-derived peptides produced during the initial stage of wound repair following elastase-mediated proteolysis action. Among the peptides generated, those having a x.G.x.x.P.G. motif upregulate (i) keratinocyte migration, (ii) endothelial cell angiogenic phenotype, (iii) fibroblast proliferation, and (iv) induction of the expression of matrix metalloproteinases, type I collagen, and tropoelastin. All of these properties could accelerate the different stages of wound repair. Elastin-derived peptides from a chemical or a proteolytic digest of insoluble elastin alone or linked to the collagen scaffold significantly improve skin wound healing and dermal regeneration in vivo in several animal models. Such a beneficial influence has been recently extended to the treatment of burn patients. In this respect, recent investigations have focused on the design of elastin-derived peptides or elastin-building blocks, as obtained from peptide chemistry or by genetic engineering, to elaborate biocompatible elastin peptides, which are considered as ideal biomaterials for "catalyzing" skin repair and regeneration following injury.
Antonicelli
Frank
F
Medicine Department-CNRS UMR MeDYC 6237, University of Reims-Champagne-Ardenne, 51 rue Cognacq Jay, Reims Cédex, France.
Bellon
Georges
G
Lorimier
Sandrine
S
Hornebeck
William
W
D043402:Cathepsin A / Q000378:metabolism; D004549:Elastin / Q000502:physiology*; D005697:Galactosides / Q000378:metabolism; D006801:Humans; D009439:Neuraminidase / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology*; D012867:Skin / Q000378:metabolism*; D012879:Skin Physiological Phenomena; D014468:Umbelliferones / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology*
D005697:Galactosides; D011956:Receptors, Cell Surface; D014468:Umbelliferones; C101993:cyclohexenoesculetin-beta-galactoside; C054901:elastin-binding proteins; D004549:Elastin; C486385:NEU1 protein, human; D009439:Neuraminidase; D043402:Cathepsin A