Small leucine-rich proteoglycans inhibit CNS regeneration by modifying the structural and mechanical properties of the lesion environment.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
26 10 2023
26 10 2023
Historique:
received:
22
02
2023
accepted:
04
10
2023
medline:
30
10
2023
pubmed:
27
10
2023
entrez:
26
10
2023
Statut:
epublish
Résumé
Extracellular matrix (ECM) deposition after central nervous system (CNS) injury leads to inhibitory scarring in humans and other mammals, whereas it facilitates axon regeneration in the zebrafish. However, the molecular basis of these different fates is not understood. Here, we identify small leucine-rich proteoglycans (SLRPs) as a contributing factor to regeneration failure in mammals. We demonstrate that the SLRPs chondroadherin, fibromodulin, lumican, and prolargin are enriched in rodent and human but not zebrafish CNS lesions. Targeting SLRPs to the zebrafish injury ECM inhibits axon regeneration and functional recovery. Mechanistically, we find that SLRPs confer mechano-structural properties to the lesion environment that are adverse to axon growth. Our study reveals SLRPs as inhibitory ECM factors that impair axon regeneration by modifying tissue mechanics and structure, and identifies their enrichment as a feature of human brain and spinal cord lesions. These findings imply that SLRPs may be targets for therapeutic strategies to promote CNS regeneration.
Identifiants
pubmed: 37884489
doi: 10.1038/s41467-023-42339-7
pii: 10.1038/s41467-023-42339-7
pmc: PMC10603094
doi:
Substances chimiques
Small Leucine-Rich Proteoglycans
0
Proteoglycans
0
Chondroitin Sulfate Proteoglycans
0
Decorin
0
Extracellular Matrix Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6814Informations de copyright
© 2023. The Author(s).
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