Planning, evaluating and vetting receptor signaling studies to assess hyaluronan size-dependence and specificity.
Planning, evaluating and vetting receptor signaling studies to assess hyaluronan size-dependence and specificity.
复制标题
规划、评估和审查受体信号传导研究，以评估透明质酸的大小依赖性和特异性。
DOI：
10.1093/glycob/cwx056
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发表时间：
2017
期刊：
影响因子：
4.3
通讯作者：
Weigel,PaulH
中科院分区：
文献类型：
--
作者：
Weigel,PaulH
在过去的40年里，透明质酸（HA）生物学的许多不同领域的令人兴奋的发现都集中在HA结合细胞表面HA受体（如CD44、Layilin、LYVE-1、HARE/Stab2和RHAMM）的能力上，有时也会激活细胞内信号转导通路，通常涉及ERK1/2。尽管令人困惑，HA介导的一些受体信号通路激活的一个主要特征是依赖于结合的HA的大小。直接与HA相互作用的受体，可能不包括TLR2/4，可以很好地与任何HA分子结合，这取决于受体。尽管它们能够结合几乎任何大小的HA，但只有特定质量范围的HA链才能激活受体介导的细胞信号传导。许多研究已经通过使用不同的：血凝素受体、细胞类型、动物模型、血凝素来源、血凝素大小、评估血凝素质量的分析和不同的对照来验证血凝素特异性或血凝素大小依赖性，证明了这一新兴故事的部分内容。最近的报道强调了透明质酸片段的潜在内毒素污染问题，特别是由透明质酸酶消化产生的内毒素污染。此外，不熟悉透明质酸多分散性的研究人员必须适应使用和解释没有独特分子质量（分子量）的制剂的数据。这些因素和其他因素所产生的困惑、不确定性和怀疑阻碍了对ha特异性和ha大小依赖性受体激活的普遍共识的发展。本文概述了问题，建议的策略和验证控制，以帮助那些计划ha介导的受体信号研究或那些试图评估文献的人。
Exciting discoveries in many diverse fields of hyaluronan (HA) biology over the last 40 years have centered around the ability of HA to bind cell surface HA receptors (e.g., CD44, Layilin, LYVE-1, HARE/Stab2 and RHAMM) and sometimes also to activate intracellular signal transduction pathways, frequently involving ERK1/2. Although perplexing, a major characteristic of HA-mediated signal pathway activation for some receptors has been a dependence on the size of the bound HA. Receptors that directly interact with HA, which may not include TLR2/4, bind very well to any HA molecule >8–20 sugars, depending on the receptor. Despite their ability to bind virtually any size HA, only HA chains of a particular mass range can activate receptor-mediated cell signaling. Many studies have demonstrated parts of this emerging story by utilizing different: HA receptors, cell types, animal models, HA sources, HA sizes, assays to assess HA mass and varying controls to verify HA specificity or HA size-dependence. Recent reports have highlighted issues with potential endotoxin contamination of HA fragments, especially those generated by hyaluronidase digestion. Also, researchers unfamiliar with HA polydispersity must adjust to working with, and interpreting data for, preparations without a unique molecular mass (molecular weight). The confusion, uncertainty and skepticism generated by these and other factors has hindered the development of a general consensus about HA-specific and HA-size dependent receptor activation. An overview of issues, suggested strategies and validating controls is presented to aid those planning an HA-mediated receptor signaling study or those trying to evaluate the literature.