Maldonado, Horacio 
ORCID: 0000-0002-7017-5215, Savage, Bryan D, Barker, Harlan R, May, Ulrike, Vähätupa, Maria, Badiani, Rahul K, Wolanska, Katarzyna I, Turner, Craig ML, Pemmari, Toini, Ketomäki, Tuomo et al (show 5 more authors)
(2023)
Systemically administered wound-homing peptide accelerates wound healing by modulating syndecan-4 function.
Nature Communications, 14 (1).
8069-.
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Systemically administered wound-homing peptide accelerates wound healing by modulating syndecan-4 function.pdf - Open Access published version Download (9MB) | Preview |
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Epidermis, Animals, Mice, Peptides, Wound Healing, Cell Movement, Male, Syndecan-4, Epidermal Cells |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 15 Jan 2024 08:42 |
| Last Modified: | 15 Jan 2024 08:42 |
| DOI: | 10.1038/s41467-023-43848-1 |
| Open Access URL: | https://www.nature.com/articles/s41467-023-44574-4 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3177828 |
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