Bibliographic Details
| Title: |
Protection of stromal cell-derived factor-1 SDF-1/CXCL12 against proteases yields improved skin wound healing |
| Authors: |
Rafaela Vaz Sousa Pereira, Mostafa EzEldeen, Estefania Ugarte-Berzal, Jennifer Vandooren, Erik Martens, Mieke Gouwy, Eva Ganseman, Jo Van Damme, Patrick Matthys, Jan Jeroen Vranckx, Paul Proost, Ghislain Opdenakker |
| Source: |
Frontiers in Immunology, Vol 15 (2024) |
| Publisher Information: |
Frontiers Media S.A., 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Immunologic diseases. Allergy |
| Subject Terms: |
SDF-1, CXCL12, proteolysis, chemokine, COAM, wound healing, Immunologic diseases. Allergy, RC581-607 |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1664-3224 |
| Relation: |
https://www.frontiersin.org/articles/10.3389/fimmu.2024.1359497/full; https://doaj.org/toc/1664-3224 |
| DOI: |
10.3389/fimmu.2024.1359497 |
| Access URL: |
https://doaj.org/article/a3beb009fdca434c94d95233677ef312 |
| Accession Number: |
edsdoj.3beb009fdca434c94d95233677ef312 |
| Database: |
Directory of Open Access Journals |
