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



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]

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Abstract

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 in vitro . 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.

Item Type: Preprint
Uncontrolled Keywords: 3101 Biochemistry and Cell Biology, 31 Biological Sciences, Wound Healing and Care, Biotechnology, 5.1 Pharmaceuticals, 2.1 Biological and endogenous factors, Skin
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: 19 Jul 2024 00:33
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