Savage, Bryan, Maldonado, Horacio 
ORCID: 0000-0002-7017-5215, May, Ulrike, Vähätupa, Maria, Barker, H ORCID: 0000-0003-4125-2522, Badiani, Rahul, Wolanska, Katarzyna, Turner, Craig, Pemmari, Toini ORCID: 0000-0002-5822-8556, Ketomaki, Tuomo et al (show 5 more authors)
(2022)
Systemically administered wound-homing peptide accelerates wound healing by modulating syndecan-4 function.
[Preprint]
Abstract
<jats:title>Abstract</jats:title> <jats:p>CAR (CARSKNKDC) is a wound-homing peptide that recognises angiogenic neovessels. Here we discover that systemically administered CAR peptide has an inherent ability to promote wound healing; wounds close and re-epithelialise faster in CAR-treated mice. CAR promotes keratinocyte migration <jats:italic>in vitro</jats:italic>. Syndecan-4 (SDC4) is a heparan sulfate proteoglycan that regulates cell migration and is crucial for wound healing. We report that SDC4 expression is restricted to epidermis and blood vessels in skin wounds. SDC4 regulates cell binding and internalisation of CAR peptide and CAR-mediated cytoskeletal remodelling. CAR induces SDC4-dependent activation of the small GTPase Arf6 (ARF6) and promotes SDC4- and ARF6-mediated keratinocyte migration. Finally, we show that genetic ablation of SDC4 in mice eliminates CAR-induced wound re-epithelialisation following systemic administration. We propose that CAR peptide activates SDC4 function to selectively promote re-epithelialisation. Thus, CAR peptide provides an entirely new therapeutic approach to enhance wound healing; systemic, yet target organ- and cell-specific.</jats:p>
| Item Type: | Preprint |
|---|---|
| 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: | 13 Oct 2022 13:27 |
| Last Modified: | 18 Jan 2023 20:36 |
| DOI: | 10.21203/rs.3.rs-1546533/v1 |
| Open Access URL: | https://assets.researchsquare.com/files/rs-1546533... |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3165422 |
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