Systemically administered wound-homing peptide accelerates wound healing by modulating syndecan-4 function

Horacio Maldonado, Bryan D. Savage, Harlan R. Barker, Ulrike May, Maria Vähätupa, Rahul K. Badiani, Katarzyna I. Wolanska, Craig M.L. Turner, Toini Pemmari, Tuomo Ketomäki, Stuart Prince, Martin J. Humphries, Erkki Ruoslahti, Mark R. Morgan, Tero A.H. Järvinen

Tutkimustuotos: ArtikkeliScientificvertaisarvioitu

2 Sitaatiot (Scopus)
19 Lataukset (Pure)

Abstrakti

CAR (CARSKNKDC) is a wound-homing peptide that recognises angiogenic neovessels. Here we discover that systemically administered CAR peptide has inherent ability to promote wound healing: wounds close and re-epithelialise faster in CAR-treated male mice. CAR promotes keratinocyte migration in vitro. The heparan sulfate proteoglycan syndecan-4 regulates cell migration and is crucial for wound healing. We report that syndecan-4 expression is restricted to epidermis and blood vessels in mice skin wounds. Syndecan-4 regulates binding and internalisation of CAR peptide and CAR-mediated cytoskeletal remodelling. CAR induces syndecan-4-dependent activation of the small GTPase ARF6, via the guanine nucleotide exchange factor cytohesin-2, and promotes syndecan-4-, ARF6- and Cytohesin-2-mediated keratinocyte migration. Finally, we show that genetic ablation of syndecan-4 in male mice eliminates CAR-induced wound re-epithelialisation following systemic administration. We propose that CAR peptide activates syndecan-4 functions to selectively promote re-epithelialisation. Thus, CAR peptide provides a therapeutic approach to enhance wound healing in mice; systemic, yet target organ- and cell-specific.

AlkuperäiskieliEnglanti
Artikkeli8069
JulkaisuNature Communications
Vuosikerta14
Numero1
DOI - pysyväislinkit
TilaJulkaistu - jouluk. 2023
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Julkaisufoorumi-taso

  • Jufo-taso 3

!!ASJC Scopus subject areas

  • Yleinen kemia
  • Yleinen biokemia, genetiikka ja molekyylibiologia
  • Yleinen fysiikka ja tähtitiede

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