A β-glucan from Grifola frondosa effectively delivers therapeutic oligonucleotide into cells via dectin-1 receptor and attenuates TNFα gene expression
A β-glucan from Grifola frondosa effectively delivers therapeutic oligonucleotide into cells via dectin-1 receptor and attenuates TNFα gene expression
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来自 Grifola frondosa 的 β-葡聚糖通过 dectin-1 受体有效地将治疗性寡核苷酸递送到细胞中并减弱 TNF α 基因表达
DOI：
10.1016/j.ijbiomac.2020.01.236
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发表时间：
2020-04-15
影响因子：
8.2
通讯作者：
Fang, Jianping
中科院分区：
文献类型：
--
作者：
Cui, Hao;Zhu, Xinying;Fang, Jianping
灰树花是一种营养价值和生物活性极高的药食两用菌。在本研究中，使用5%的冷NaOH从灰树花子实体中纯化出具有5.42 × 10（6）Da的高分子量的可溶性均质β-葡聚糖GFPS。GFPS的结构用FT-IR、NMR和单糖组成分析来确定，并且被鉴定为在每三个残基上具有在C-6处分支的单个β-D-（1-6）-连接的吡喃葡萄糖残基的β-D-（1-3）-连接的葡聚糖主链。结果表明，GFPS具有三股螺旋结构，并能与多聚脱氧腺苷酸（poly[A]）形成复合物。进一步的研究表明GFPS可以与设计的靶向促炎细胞因子TNF α（TNF α-A60）初级转录物的反义寡核苷酸（阿索）的poly[A]部分相互作用。这种基于GFP的复合物可以通过dectin-1受体将TNF α-A60掺入巨噬细胞中，并减弱脂多糖诱导的TNF α分泌。我们的研究结果表明，GFPS可用于递送治疗性寡核苷酸，用于治疗炎症和癌症等疾病。(C)2020爱思唯尔B. V.保留所有权利。
Grifola frondosa is an edible and medicinal mushroom with great nutritional values and bioactivities. In the present study, a soluble homogeneous beta-glucan, GFPS, with high molecular mass of 5.42 x 10(6) Da was purified from the fruit bodies of Grifola frondosa using 5% cold NaOH. The structure of GFPS was determined with FT-IR, NMR, and monosaccharide composition analysis, and was identified to be a beta-D-(1-3)-linked glucan backbone with a single beta-D-(1-6)-linked glucopyranosyl residue branched at C-6 on every third residue. Our results indicated that GFPS had a triple helical structure and could form complex with polydeoxyadenylic acid (poly[A]). Further studies demonstrated that GFPS could interact with poly[A] moiety of a designed antisense oligonudeotide (ASO) targeting the primary transcript of proinflammatory cytokine TNF alpha (TNF alpha-A60). This GFPS-based complex could incorporate TNF alpha-A60 into the macrophage cells via dectin-1 receptor and attenuate lipopolysaccharide-induced secretion of TNF alpha. Our results suggested that GFPS could be applied to deliver therapeutic oligonucleotides for the treatment of diseases such as inflammation and cancers. (C) 2020 Elsevier B.V. All rights reserved.