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. J. Turner, Toini Pemmari, Tuomo Ketomäki, Stuart Prince, Martin J. Humphries, Erkki Ruoslahti, Mark R. Morgan () and Tero A. H. Järvinen ()
Additional contact information
Horacio Maldonado: University of Liverpool
Bryan D. Savage: University of Liverpool
Harlan R. Barker: Tampere University & Tampere University Hospital
Ulrike May: Tampere University & Tampere University Hospital
Maria Vähätupa: Tampere University & Tampere University Hospital
Rahul K. Badiani: University of Liverpool
Katarzyna I. Wolanska: University of Liverpool
Craig M. J. Turner: University of Liverpool
Toini Pemmari: Tampere University & Tampere University Hospital
Tuomo Ketomäki: Tampere University & Tampere University Hospital
Stuart Prince: Tampere University & Tampere University Hospital
Martin J. Humphries: University of Manchester
Erkki Ruoslahti: University of California (UCSB)
Mark R. Morgan: University of Liverpool
Tero A. H. Järvinen: Tampere University & Tampere University Hospital

Nature Communications, 2023, vol. 14, issue 1, 1-23

Abstract: Abstract 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.

Date: 2023
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-43848-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43848-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-43848-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().