Biochemistry, Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Greece.
Department of Medicine and Surgery, University of Insubria, Varese, Italy.
FEBS J. 2019 Aug;286(15):2883-2908. doi: 10.1111/febs.14777. Epub 2019 Feb 21.
Hyaluronan (HA) is a linear nonsulfated glycosaminoglycan of the extracellular matrix that plays a pivotal role in a variety of biological processes. High-molecular weight HA exhibits different biological properties than oligomers and low-molecular weight HA. Depending on their molecular size, HA fragments can influence cellular behavior in a different mode of action. This phenomenon is attributed to the different manner of interaction with the HA receptors, especially CD44 and RHAMM. Both receptors can trigger signaling cascades that regulate cell functional properties, such as proliferation migration, angiogenesis, and wound healing. HA fragments are able to enhance or attenuate the HA receptor-mediated signaling pathways, as they compete with the endogenous HA for binding to the receptors. The modulation of these pathways could be crucial for the development of pathological conditions, such as inflammation and cancer. The primary goal of this review is to critically present the importance of HA molecular size on cellular signaling, functional cell properties, and morphology in normal and pathological conditions, including inflammation and cancer. A deeper understanding of these mechanisms could contribute to the development of novel therapeutic strategies.
透明质酸（HA）是细胞外基质中的一种线性非硫酸化糖胺聚糖，在多种生物学过程中发挥着关键作用。高分子量的 HA 表现出与低聚物和低分子量 HA 不同的生物学特性。根据其分子大小，HA 片段可以以不同的作用方式影响细胞行为。这种现象归因于与 HA 受体（尤其是 CD44 和 RHAMM）不同的相互作用方式。这两种受体都可以触发信号级联反应，调节细胞的功能特性，如增殖、迁移、血管生成和伤口愈合。HA 片段能够增强或减弱 HA 受体介导的信号通路，因为它们与内源性 HA 竞争与受体结合。这些途径的调节对于炎症和癌症等病理状况的发展可能至关重要。本综述的主要目的是批判性地阐述 HA 分子大小对正常和病理条件（包括炎症和癌症）下细胞信号、功能细胞特性和形态的重要性。对这些机制的深入了解可能有助于开发新的治疗策略。
