Melrose James
Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2052, Australia.
Raymond Purves Bone and Joint Research Laboratories, Kolling Institute of Medical Research, Northern Sydney Local Health District, Royal North Shore Hospital, St. Leonards, NSW 2065, Australia.
Int J Mol Sci. 2025 Mar 12;26(6):2554. doi: 10.3390/ijms26062554.
Glycosaminoglycans (GAGs) are a diverse family of ancient biomolecules that evolved over millennia as key components in the glycocalyx that surrounds all cells. GAGs have molecular recognition and cell instructive properties when attached to cell surface and extracellular matrix (ECM) proteoglycans (PGs), which act as effector molecules that regulate cellular behavior. The perception of mechanical cues which arise from perturbations in the ECM microenvironment allow the cell to undertake appropriate biosynthetic responses to maintain ECM composition and tissue function. ECM PGs substituted with GAGs provide structural support to weight-bearing tissues and an ability to withstand shear forces in some tissue contexts. This review outlines the structural complexity of GAGs and the diverse functional properties they convey to cellular and ECM PGs. PGs have important roles in cartilaginous weight-bearing tissues and fibrocartilages subject to tension and high shear forces and also have important roles in vascular and neural tissues. Specific PGs have roles in synaptic stabilization and convey specificity and plasticity in the regulation of neurophysiological responses in the CNS/PNS that control tissue function. A better understanding of GAG instructional roles over cellular behavior may be insightful for the development of GAG-based biotherapeutics designed to treat tissue dysfunction in disease processes and in novel tissue repair strategies following trauma. GAGs have a significant level of sophistication over the control of cellular behavior in many tissue contexts, which needs to be fully deciphered in order to achieve a useful therapeutic product. GAG biotherapeutics offers exciting opportunities in the modern glycomics arena.
糖胺聚糖（GAGs）是一类多样的古老生物分子，历经数千演化，成为包围所有细胞的糖萼的关键组成部分。当GAGs附着于细胞表面和细胞外基质（ECM）蛋白聚糖（PGs）时，具有分子识别和细胞指导特性，而这些PGs作为调节细胞行为的效应分子发挥作用。对ECM微环境扰动产生的机械信号的感知，使细胞能够进行适当的生物合成反应，以维持ECM组成和组织功能。被GAGs取代的ECM PGs为承重组织提供结构支持，并在某些组织环境中具备承受剪切力的能力。本综述概述了GAGs的结构复杂性以及它们赋予细胞和ECM PGs的多样功能特性。PGs在承受重量的软骨组织和承受张力及高剪切力的纤维软骨中发挥重要作用，在血管和神经组织中也具有重要作用。特定的PGs在突触稳定中发挥作用，并在中枢神经系统/外周神经系统中调节神经生理反应以控制组织功能时传递特异性和可塑性。更好地理解GAGs对细胞行为的指导作用，对于开发旨在治疗疾病过程中组织功能障碍和创伤后新型组织修复策略的基于GAGs的生物疗法可能具有启发性。在许多组织环境中，GAGs对细胞行为的控制具有高度复杂性，为了获得有用的治疗产品，需要对其进行全面解读。GAG生物疗法在现代糖组学领域提供了令人兴奋的机会。
