Wang Xiaoyun, Liu Xiaojun, Li Chao, Li Jiangtao, Qiu Meng, Wang Yongliang, Han Wenwei
College of Life Science and Health, University of Health and Rehabilitation Sciences, Qingdao, 266113, China; Qingdao Municipal Hospital, University of Health and Rehabilitation Sciences, Qingdao, 266024, China; Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, and College of Chemistry and Chemical Engineering, Ocean University of China, Qingdao, 266100, China.
College of Life Science and Health, University of Health and Rehabilitation Sciences, Qingdao, 266113, China; Qingdao Municipal Hospital, University of Health and Rehabilitation Sciences, Qingdao, 266024, China.
Carbohydr Res. 2025 Jun;552:109472. doi: 10.1016/j.carres.2025.109472. Epub 2025 Mar 28.
Hyaluronic acid (HA), the only non-sulfated glycosaminoglycan (GAG), is essential for maintaining the extracellular matrix's structural and functional integrity. Its bioactivity is determined by interactions between HA fragments of different molecular weights and specific receptors, which influence downstream signaling pathways. This review systematic summarizes the correlation between HA molecular weight dynamic changes and bioactivities focusing on imbalance of HA degradation and metabolism due to various pathological processes. Outline the core transduction mechanisms of HA receptors and signaling pathways, and innovatively hypothesize that discrepancies in cellular distribution with HA-molecular weights dependent lead to the activation of different signaling pathways from the perspective of molecular weight affecting cellular distribution. Finally, it addresses challenges in studying HA's biofunctions and provides new perspectives for future research.
透明质酸（HA）是唯一一种非硫酸化的糖胺聚糖（GAG），对于维持细胞外基质的结构和功能完整性至关重要。其生物活性由不同分子量的HA片段与特定受体之间的相互作用决定，这些相互作用会影响下游信号通路。本综述系统总结了HA分子量动态变化与生物活性之间的相关性，重点关注由于各种病理过程导致的HA降解和代谢失衡。概述了HA受体和信号通路的核心转导机制，并创新性地提出，从分子量影响细胞分布的角度来看，依赖于HA分子量的细胞分布差异会导致不同信号通路的激活。最后，探讨了研究HA生物功能所面临的挑战，并为未来研究提供了新的视角。
