Proteoglycan 4 (PRG4) treatment enhances wound closure and tissue regeneration.


Journal

NPJ Regenerative medicine
ISSN: 2057-3995
Titre abrégé: NPJ Regen Med
Pays: United States
ID NLM: 101699846

Informations de publication

Date de publication:
24 Jun 2022
Historique:
received: 15 07 2021
accepted: 20 05 2022
entrez: 24 6 2022
pubmed: 25 6 2022
medline: 25 6 2022
Statut: epublish

Résumé

The wound healing response is one of most primitive and conserved physiological responses in the animal kingdom, as restoring tissue integrity/homeostasis can be the difference between life and death. Wound healing in mammals is mediated by immune cells and inflammatory signaling molecules that regulate tissue resident cells, including local progenitor cells, to mediate closure of the wound through formation of a scar. Proteoglycan 4 (PRG4), a protein found throughout the animal kingdom from fish to elephants, is best known as a glycoprotein that reduces friction between articulating surfaces (e.g. cartilage). Previously, PRG4 was also shown to regulate the inflammatory and fibrotic response. Based on this, we asked whether PRG4 plays a role in the wound healing response. Using an ear wound model, topical application of exogenous recombinant human (rh)PRG4 hastened wound closure and enhanced tissue regeneration. Our results also suggest that rhPRG4 may impact the fibrotic response, angiogenesis/blood flow to the injury site, macrophage inflammatory dynamics, recruitment of immune and increased proliferation of adult mesenchymal progenitor cells (MPCs) and promoting chondrogenic differentiation of MPCs to form the auricular cartilage scaffold of the injured ear. These results suggest that PRG4 has the potential to suppress scar formation while enhancing connective tissue regeneration post-injury by modulating aspects of each wound healing stage (blood clotting, inflammation, tissue generation and tissue remodeling). Therefore, we propose that rhPRG4 may represent a potential therapy to mitigate scar and improve wound healing.

Identifiants

pubmed: 35750773
doi: 10.1038/s41536-022-00228-5
pii: 10.1038/s41536-022-00228-5
pmc: PMC9232611
doi:

Types de publication

Journal Article

Langues

eng

Pagination

32

Subventions

Organisme : Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada (Conseil de Recherches en Sciences Naturelles et en Génie du Canada)
ID : RGPIN-2014-04586
Organisme : Canada Foundation for Innovation (Fondation canadienne pour l'innovation)
ID : JELF
Organisme : Calgary Foundation (CF)
ID : Grace Glaum Professorship
Organisme : Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)
ID : 01309MOP-311542-DIB-CBBA-170939
Organisme : UCalgary | Cumming School of Medicine, University of Calgary (Cumming School of Medicine)
ID : PDF award

Informations de copyright

© 2022. The Author(s).

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Auteurs

Roman J Krawetz (RJ)

McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, AB, Canada. rkrawetz@ucalgary.ca.
Biomedical Engineering Graduate Program, University of Calgary, Calgary, AB, Canada. rkrawetz@ucalgary.ca.
Department of Surgery, University of Calgary, Calgary, AB, Canada. rkrawetz@ucalgary.ca.
Department Cell Biology and Anatomy, University of Calgary, Calgary, AB, Canada. rkrawetz@ucalgary.ca.

Saleem Abubacker (S)

McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, AB, Canada.

Catherine Leonard (C)

McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, AB, Canada.

Anand O Masson (AO)

McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, AB, Canada.
Biomedical Engineering Graduate Program, University of Calgary, Calgary, AB, Canada.

Sophia Shah (S)

McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, AB, Canada.
Biomedical Engineering Graduate Program, University of Calgary, Calgary, AB, Canada.

Nadia Narendran (N)

McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, AB, Canada.

Pankaj Tailor (P)

McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, AB, Canada.

Suresh C Regmi (SC)

Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada.

Elodie Labit (E)

Department of Comparative Biology and Experimental Medicine, University of Calgary, Calgary, AB, Canada.

Nicoletta Ninkovic (N)

McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, AB, Canada.
Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, Canada.

Jessica May Corpuz (JM)

McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, AB, Canada.
Biomedical Engineering Graduate Program, University of Calgary, Calgary, AB, Canada.

Kenichi Ito (K)

Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, Canada.

T Michael Underhill (TM)

Department of Cellular and Physiological Sciences and Biomedical Research Centre, University of British Columbia, Vancouver, BC, Canada.

Paul T Salo (PT)

McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, AB, Canada.
Department of Surgery, University of Calgary, Calgary, AB, Canada.

Tannin A Schmidt (TA)

McCaig Institute for Bone & Joint Health, University of Calgary, Calgary, AB, Canada.
Faculty of Kinesiology, University of Calgary, Calgary, AB, Canada.
Biomedical Engineering Department, University of Connecticut Health Center, Farmington, CT, USA.

Jeff A Biernaskie (JA)

Department of Comparative Biology and Experimental Medicine, University of Calgary, Calgary, AB, Canada.
Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada.

Classifications MeSH