Moretto Paola, Karousou Evgenia, Viola Manuela, Caon Ilaria, D'Angelo Maria Luisa, De Luca Giancarlo, Passi Alberto, Vigetti Davide
Department of Surgical and Morphological Sciences, University of Insubria, 21100 Varese, Italy.
J Diabetes Res. 2015;2015:167283. doi: 10.1155/2015/167283. Epub 2015 Mar 5.
Cell microenvironment has a critical role determining cell fate and modulating cell responses to injuries. Hyaluronan (HA) is a ubiquitous extracellular matrix glycosaminoglycan that can be considered a signaling molecule. In fact, interacting with several cell surface receptors can deeply shape cell behavior. In vascular biology, HA triggers smooth muscle cells (SMCs) dedifferentiation which contributes to vessel wall thickening. Furthermore, HA is able to modulate inflammation by altering the adhesive properties of endothelial cells. In hyperglycemic conditions, HA accumulates in vessels and can contribute to the diabetic complications at micro- and macrovasculature. Due to the pivotal role in favoring atherogenesis and neointima formation after injuries, HA could be a new target for cardiovascular pathologies. This review will focus on the recent findings regarding the regulation of HA synthesis in human vascular SMCs. In particular, the effects of the intracellular HA substrates availability, adenosine monophosphate-activated protein kinase (AMPK), and protein O-GlcNAcylation on the main HA synthetic enzyme (i.e., HAS2) will be discussed.
细胞微环境在决定细胞命运和调节细胞对损伤的反应中起着关键作用。透明质酸（HA）是一种普遍存在的细胞外基质糖胺聚糖，可被视为一种信号分子。事实上，与多种细胞表面受体相互作用可深刻影响细胞行为。在血管生物学中，HA触发平滑肌细胞（SMC）去分化，这有助于血管壁增厚。此外，HA能够通过改变内皮细胞的黏附特性来调节炎症。在高血糖条件下，HA在血管中积累，并可能导致微血管和大血管的糖尿病并发症。由于在损伤后促进动脉粥样硬化和新生内膜形成中起关键作用，HA可能成为心血管疾病的新靶点。本综述将聚焦于人类血管平滑肌细胞中HA合成调控的最新研究发现。特别是，将讨论细胞内HA底物可用性、腺苷单磷酸激活蛋白激酶（AMPK）和蛋白质O-连接N-乙酰葡糖胺化对主要HA合成酶（即HAS2）的影响。
