Bocquet Olivier, Tembely Dignê, Rioult Damien, Terryn Christine, Romier Béatrice, Bennasroune Amar, Blaise Sébastien, Sartelet Hervé, Martiny Laurent, Duca Laurent, Maurice Pascal
UMR CNRS 7369 Matrice Extracellulaire Et Dynamique Cellulaire (MEDyC), Université de Reims Champagne Ardenne (URCA), UFR Sciences Exactes Et Naturelles, Moulin de La Housse, BP1039, 51687, Reims cedex 2, France.
Plateau Technique Mobile de Cytométrie Environnementale MOBICYTE, URCA/INERIS, Université de Reims Champagne Ardenne (URCA), UFR Sciences Exactes Et Naturelles, Reims, France.
Cell Biosci. 2021 Dec 13;11(1):206. doi: 10.1186/s13578-021-00718-x.
Vascular aging is associated with remodeling of elastin, one of the main extracellular matrix component of the arterial wall, and production of elastin-derived peptides (EDP). These extracellular matrix degradation products have been shown to trigger biological activities through the elastin receptor complex (ERC) and data from the last decade have brought significant insights on the critical role played by its NEU1 subunit in the biological effects mediated by EDP and the ERC in vascular and metabolic diseases.
Using a proteomic approach, we previously identified new potential interaction partners of membrane NEU1. Here, we validated the interaction between NEU1 and the β integrin in human monocytes and show that binding of EDP to the ERC leads to desialylation of β integrin through NEU1. A similar action mechanism was identified in human umbilical vein endothelial cells (HUVEC) for intercellular cell adhesion molecule-1 (ICAM-1). Importantly, these effects were associated with a significant increase in monocyte adhesion to endothelial cells and monocyte transendothelial migration.
These results demonstrate that membrane NEU1 sialidase interacts and modulates the sialylation levels of the β integrin and ICAM-1 through the ERC in monocytes and endothelial cells, respectively, and suggest that EDP and the ERC, through this newly identified common mode of action governed by NEU1, may be important regulators of circulating monocyte recruitment to inflamed vascular sites. Moreover, by its ability to interact with and to modulate the sialylation of key membrane glycoproteins through NEU1, new biological functions are anticipated for EDP and the ERC in elastin remodeling-associated disorders.
血管老化与弹性蛋白重塑有关，弹性蛋白是动脉壁主要的细胞外基质成分之一，同时也与弹性蛋白衍生肽（EDP）的产生有关。这些细胞外基质降解产物已被证明可通过弹性蛋白受体复合物（ERC）触发生物活性，过去十年的数据为其NEU1亚基在血管和代谢疾病中EDP和ERC介导的生物学效应中所起的关键作用带来了重要见解。
我们先前使用蛋白质组学方法鉴定了膜NEU1的新潜在相互作用伙伴。在此，我们验证了NEU1与人单核细胞中β整合素之间的相互作用，并表明EDP与ERC的结合通过NEU1导致β整合素去唾液酸化。在人脐静脉内皮细胞（HUVEC）中，细胞间黏附分子-1（ICAM-1）也发现了类似的作用机制。重要的是，这些效应与单核细胞对内皮细胞的黏附及单核细胞跨内皮迁移的显著增加有关。
这些结果表明，膜NEU1唾液酸酶分别通过ERC在单核细胞和内皮细胞中与β整合素和ICAM-1相互作用并调节其唾液酸化水平，这表明EDP和ERC通过这种新发现的由NEU1控制的共同作用模式，可能是循环单核细胞募集到炎症血管部位的重要调节因子。此外，由于EDP和ERC能够通过NEU1与关键膜糖蛋白相互作用并调节其唾液酸化，预计它们在弹性蛋白重塑相关疾病中具有新的生物学功能。
