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High molecular weight form of hyaluronic acid reduces neuroinflammatory response in injured sciatic nerve via the intracellular domain of CD44
Journal of Biomedical Materials Research Part B: Applied Biomaterials ( IF 3.4 ) Pub Date : 2020-09-14 , DOI: 10.1002/jbm.b.34731
I‐Ming Jou, Tung‐Tai Wu, Che‐Chia Hsu, Cheng‐Chang Yang, Jhy‐Shrian Huang, Yuan‐Kun Tu, Jung‐Shun Lee, Fong‐Chin Su, Yao‐Lung Kuo

Inflammatory response after peripheral nerve injury is required for clearance of tissue debris and effective regeneration. Studies have revealed that hyaluronic acid (HA) may exert different properties depending on their molecular size. High molecular weight HA (>>1,000 kDa; HMW‐HA) displays immunosuppressive properties, whereas low molecular weight HA (<800 kDa; LMW‐HA) induces proinflammatory responses. The role of HMW‐HA interaction with CD44, a major HA receptor, in neuroinflammatory responses has not been fully elucidated. The purpose of this experimental study was to investigate the effects of topical applications of HMW‐HA on the sciatic nerve injury in an adult rat model. At the crush site on the sciatic nerve, the recordings of compound muscle action potential (CMAP) and the levels of several proteins related to inflammatory response were assessed at time intervals of 2, 4, and 6 weeks postsurgery. Here, we show that the recovery effect of HMW‐HA treatment had significantly shortened latency and increased amplitude of CMAP compared with crushed alone, crushed plus γ‐secretase inhibitor with or without HA treatment at 6 weeks after surgery. Our data reveal that HMW‐HA could downregulate the expression of IL1‐β, TLR4, and MMP‐9, whereas these proteins expression were increased when the CD44‐ICD activity was inhibited using γ‐secretase inhibitor. Our findings demonstrated a novel role of CD44‐ICD in HA‐mediated recovery of peripheral nerve injury. Clinical relevance: an alternative for the regeneration of peripheral nerve injury.

中文翻译:

高分子量形式的透明质酸通过 CD44 的细胞内结构域降低受损坐骨神经的神经炎症反应

周围神经损伤后的炎症反应是清除组织碎片和有效再生所必需的。研究表明,透明质酸 (HA) 可能会根据其分子大小发挥不同的特性。高分子量 HA ( >>1,000 kDa;HMW-HA) 表现出免疫抑制特性,而低分子量 HA (<800 kDa; LMW-HA) 诱导促炎反应。HMW-HA 与主要 HA 受体 CD44 相互作用在神经炎症反应中的作用尚未完全阐明。本实验研究的目的是研究局部应用 HMW-HA 对成年大鼠模型坐骨神经损伤的影响。在坐骨神经的挤压部位,以术后 2、4 和 6 周的时间间隔评估复合肌肉动作电位 (CMAP) 的记录和与炎症反应相关的几种蛋白质的水平。在这里,我们表明,与单独粉碎相比,HMW-HA 处理的恢复效果显着缩短了潜伏期并增加了 CMAP 的幅度,术后 6 周粉碎加 γ-分泌酶抑制剂加或不加 HA 治疗。我们的数据显示,HMW-HA 可以下调 IL1-β、TLR4 和 MMP-9 的表达,而当使用 γ-分泌酶抑制剂抑制 CD44-ICD 活性时,这些蛋白质的表达增加。我们的研究结果证明了 CD44-ICD 在 HA 介导的周围神经损伤恢复中的新作用。临床相关性:周围神经损伤再生的替代方法。
更新日期:2020-09-14
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