Mesoglycan connects Syndecan-4 and VEGFR2 through Annexin A1 and formyl peptide receptors to promote angiogenesis in vitro.
Mesoglycan connects Syndecan-4 and VEGFR2 through Annexin A1 and formyl peptide receptors to promote angiogenesis in vitro.
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DOI：
10.1111/febs.16043
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发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Petrella A
中科院分区：
文献类型：
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作者：
Pessolano E;Belvedere R;Novizio N;Filippelli A;Perretti M;Whiteford J;Petrella A
中聚糖是具有纤维蛋白溶解作用和增强皮肤伤口修复潜力的糖胺聚糖（GAG）的混合物。在这里，我们使用从野生型（WT）和Syndecan-4 null（Sdc 4-/-）C57 BL/6小鼠中分离的内皮细胞来证明中聚糖促进细胞运动和体外血管生成作用于共受体Syndecan-4（SDC 4）。已知后者参与细胞外囊泡（EV）的形成和释放。我们表征了由HUVEC释放的EV，并评估了它们对血管生成的影响。特别地，我们专注于含有膜联蛋白A1（ANXA 1）的EV，因为它们可能通过与甲酰肽受体（FPRs）的相互作用而有助于管形成。在我们的模型中，ANXA 1-FPRs键刺激血管内皮生长因子（VEGF-A）的释放，该因子与血管内皮受体-2（VEGFR 2）相互作用，并激活以自分泌方式增强细胞运动的途径，如伤口愈合/侵袭试验所示，以及诱导内皮细胞向间充质细胞转化（EndMT）。因此，我们首次证明了中聚糖在愈合过程中发挥其促血管生成作用，触发三个相互关联的分子轴的激活：中聚糖-SDC 4，EVs-ANXA 1-FPRs和VEGF-A-VEGFR 2。给予内皮细胞的中聚糖与Syndecan-4（SDC 4）相互作用，这导致含有蛋白膜联蛋白A1（ANXA 1）的囊泡的形成和分泌增加。ANXA 1通过细胞外囊泡（EV）释放，以自分泌方式与甲酰基肽受体（FPR）相互作用。这种相互作用促进血管内皮生长因子（VEGF）的释放，其结合其受体VEGFR 2，增强内皮细胞中的促血管生成活性。
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. The mesoglycan administered to endothelial cells interacts with Syndecan‐4 (SDC4) and this causes an increase in formation and secretion of vesicles containing the protein Annexin A1 (ANXA1). ANXA1, released through extracellular vesicles (EVs), interacts with Formyl peptide receptors (FPRs) in an autocrine way. This interaction promotes the release of Vascular endothelial growth factor (VEGF), which binds its receptor VEGFR2 enhancing the pro‐angiogenic activity in endothelial cells.
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DOI：
10.1073/pnas.1521230113
发表时间：
2016-02-23
影响因子：
11.1
作者：
Kowal, Joanna;Arras, Guillaume;Thery, Clotilde
通讯作者：
Thery, Clotilde
影响因子：
4.1
作者：
Abhinand, Chandran S.;Raju, Rajesh;Sudhakaran, Perumana R.
通讯作者：
Sudhakaran, Perumana R.
影响因子：
5
作者：
Belvedere, Raffaella;Pessolano, Emanuela;Petrella, Antonello
通讯作者：
Petrella, Antonello
影响因子：
5.5
作者：
Becsky D;Szabo K;Gyulai-Nagy S;Gajdos T;Bartos Z;Balind A;Dux L;Horvath P;Erdelyi M;Homolya L;Keller-Pinter A
通讯作者：
Keller-Pinter A
影响因子：
82.9
作者：
通讯作者：
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