Evidence map›Paper›PMID 38057316›Full record

ArticleNature communications2023

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 and 5 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.8field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 20 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Spatial and Functional Roles of Syndecans in Skin Wound Healing.International journal of molecular sciences · 2025
    Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Microneedle-Mediated Delivery of Extracellular Matrix-Inspired Peptides for Mitigation of Burn Wound Progression and Support of Tissue Repair.Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 3 countries.

Horacio MaldonadoInstitute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool, UK.ORCID 0000-0002-7017-5215
Bryan D SavageInstitute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool, UK.
Harlan R BarkerFaculty of Medicine and Health Technology, Tampere University & Tampere University Hospital, Tampere, Finland.ORCID 0000-0003-4125-2522
Ulrike MayFaculty of Medicine and Health Technology, Tampere University & Tampere University Hospital, Tampere, Finland.
Maria VähätupaFaculty of Medicine and Health Technology, Tampere University & Tampere University Hospital, Tampere, Finland.
Rahul K BadianiInstitute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool, UK.
Katarzyna I WolanskaInstitute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool, UK.ORCID 0000-0002-2990-0710
Craig M J TurnerInstitute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool, UK.
Toini PemmariFaculty of Medicine and Health Technology, Tampere University & Tampere University Hospital, Tampere, Finland.
Tuomo KetomäkiFaculty of Medicine and Health Technology, Tampere University & Tampere University Hospital, Tampere, Finland.
Stuart PrinceFaculty of Medicine and Health Technology, Tampere University & Tampere University Hospital, Tampere, Finland.
Martin J HumphriesWellcome Trust Centre for Cell-Matrix Research, University of Manchester, Manchester, UK.ORCID 0000-0002-4331-6967
Erkki RuoslahtiCancer Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA and Center for Nanomedicine, University of California (UCSB), Santa Barbara, CA, USA.
Mark R MorganInstitute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool, UK. mark.morgan@liverpool.ac.uk.ORCID 0000-0001-7728-9883
Tero A H JärvinenFaculty of Medicine and Health Technology, Tampere University & Tampere University Hospital, Tampere, Finland. tero.jarvinen@tuni.fi.ORCID 0000-0002-4027-1759
Tampere University Hospital · FIUniversity of Liverpool · GBSanford Burnham Prebys Medical Discovery Institute · USWellcome Centre for Cell-Matrix Research · GB

Funding

Wellcome TrustWellcome Trust 092015
6 · The paper itself

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.

Indexed as

Syndecan-4Wound HealingAnimalsCell MovementEpidermal CellsEpidermisMaleMicePeptidesPeptidesSyndecan-4

Identifiers

PMID38057316
PMCPMC10700342
OpenAlexW4389392699

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.