Protection of stromal cell-derived factor-1 SDF-1/CXCL12 against proteases yields improved skin wound healing.
Front Immunol
; 15: 1359497, 2024.
Article
em En
| MEDLINE
| ID: mdl-39156898
ABSTRACT
SDF-1/CXCL12 is a unique chemotactic factor with multiple functions on various types of precursor cells, all carrying the cognate receptor CXCR4. Whereas individual biological functions of SDF-1/CXCL12 have been well documented, practical applications in medicine are insufficiently studied. This is explained by the complex multifunctional biology of SDF-1 with systemic and local effects, critical dependence of SDF-1 activity on aminoterminal proteolytic processing and limited knowledge of applicable modulators of its activity. We here present new insights into modulation of SDF-1 activity in vitro and in vivo by a macromolecular compound, chlorite-oxidized oxyamylose (COAM). COAM prevented the proteolytic inactivation of SDF-1 by two inflammation-associated proteases matrix metalloproteinase-9/MMP-9 and dipeptidylpeptidase IV/DPPIV/CD26. The inhibition of proteolytic inactivation was functionally measured by receptor-mediated effects, including intracellular calcium mobilization, ERK1/2 phosphorylation, receptor internalization and chemotaxis of CXCR4-positive cells. Protection of SDF-1/CXCL12 against proteolysis was dependent on electrostatic COAM-SDF-1 interactions. By in vivo experiments in mice, we showed that the combination of COAM with SDF-1 delivered through physiological fibrin hydrogel had beneficial effect for the healing of skin wounds. Collectively, we show that COAM protects SDF-1 from proteolytic inactivation, maintaining SDF-1 biological activities. Thus, protection from proteolysis by COAM represents a therapeutic strategy to prolong SDF-1 bioavailability for wound healing applications.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pele
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Cicatrização
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Dipeptidil Peptidase 4
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Receptores CXCR4
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Quimiocina CXCL12
Limite:
Animals
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Humans
Idioma:
En
Revista:
Front Immunol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Bélgica