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Mesoglycan connects Syndecan‐4 and VEGFR2 through Annexin A1 and formyl peptide receptors to promote angiogenesis in vitro
Author(s) -
Pessolano Emanuela,
Belvedere Raffaella,
Novizio Nunzia,
Filippelli Amelia,
Perretti Mauro,
Whiteford James,
Petrella Antonello
Publication year - 2021
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.16043
Subject(s) - angiogenesis , syndecan 1 , wound healing , receptor , paracrine signalling , microbiology and biotechnology , cancer research , annexin a2 , annexin , vascular endothelial growth factor , autocrine signalling , cell migration , motility , biology , pharmacology , chemistry , cell , immunology , vegf receptors , biochemistry
Mesoglycan is a mixture of glycosaminoglycans (GAG) with fibrinolytic effects and the potential to enhance skin wound repair. Here, we have used endothelial cells isolated from wild‐type (WT) and Syndecan‐4 null (Sdc4‐/‐) C57BL/6 mice to demonstrate that mesoglycan promotes cell motility and in vitro angiogenesis acting on the co‐receptor Syndecan‐4 (SDC4). This latter is known to participate in the formation and release of extracellular vesicles (EVs). We characterized EVs released by HUVECs and assessed their effect on angiogenesis. Particularly, we focused on Annexin A1 (ANXA1) containing EVs, since they may contribute to tube formation via interactions with Formyl peptide receptors (FPRs). In our model, the bond ANXA1‐FPRs stimulates the release of vascular endothelial growth factor (VEGF‐A) that interacts with vascular endothelial receptor‐2 (VEGFR2) and activates the pathway enhancing cell motility in an autocrine manner, as shown by wound healing/invasion assays, and the induction of endothelial to mesenchymal transition (EndMT). Thus, we have shown for the first time that mesoglycan exerts its pro‐angiogenic effects in the healing process triggering the activation of the three interconnected molecular axis: mesoglycan‐SDC4, EVs‐ANXA1‐FPRs, and VEGF‐A‐VEGFR2.