Hyaluronan goes to great length.

IF 4.1 Q2 CELL BIOLOGY Cell Stress Pub Date : 2020-07-17 DOI:10.15698/cst2020.09.231
Vera Gorbunova, Masaki Takasugi, Andrei Seluanov
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引用次数: 6

Abstract

Hyaluronan is a major non-protein component of extracellular matrix that affects biomechanical properties of tissues and interacts with cell receptors. Hyaluronan is a linear glycosaminoglycan composed of repeating disaccharides of (β, 1-4)-glucuronic acid (GlcUA) and (β, 1-3)-N-acetyl glucosamine (GlcNAc). The length of hyaluronan can range from an oligomer to an extremely long form up to millions of daltons. The concept that emerged in the field is that high (HMW-HA) and low (LMW-HA) molecular weight hyaluronans have different biological properties and trigger different signaling cascades within the cells. LMW-HA is associated with inflammation, tissue injury and metastasis, while HMW-HA improves tissue homeostasis and has anti-inflammatory and antimetastatic properties. HMW-HA is used in the clinic to treat arthritis, and as a filler in surgery and in the form of rinses to treat local inflammation. However, HMW-HA products used in the clinic come in a range of sizes between 0.5-6 mDa that are used interchangeably. Remarkably, the tissues of a long-lived and cancer-resistant rodent, the naked mole rat, contain abundant HA of very high molecular weight. While human fibroblasts secrete HA up to 2 MDa, naked mole rat fibroblasts produce HA of 6-12 MDa. Does this very high HMW-HA (vHMW-HA) differ functionally from HMW-HA? We found that vHMW-HA has superior cytoprotective properties compared to HMW-HA, and interacts differently with the CD44 receptor leading to distinct transcriptional changes (Takasugi et al. (2020), Nat Commun). These results indicate that vHMW-HA has greater therapeutic benefits than the standard HMW-HA.

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透明质酸的作用很长。
透明质酸是细胞外基质的主要非蛋白成分,影响组织的生物力学特性并与细胞受体相互作用。透明质酸是由(β, 1-4)-葡萄糖醛酸(GlcUA)和(β, 1-3)- n -乙酰氨基葡萄糖(GlcNAc)的重复双糖组成的线性糖胺聚糖。透明质酸的长度可以从低聚物到极长的形式,最长可达数百万道尔顿。该领域出现的概念是,高(HMW-HA)和低(LMW-HA)分子量透明质酸具有不同的生物学特性,并在细胞内触发不同的信号级联。低分子量ha与炎症、组织损伤和转移有关,而低分子量ha可改善组织稳态,具有抗炎和抗转移特性。HMW-HA在临床上用于治疗关节炎,在手术中用作填充物,并以冲洗的形式用于治疗局部炎症。然而,临床使用的HMW-HA产品的大小范围在0.5-6 mDa之间,可以互换使用。值得注意的是,一种长寿且抗癌的啮齿动物裸鼹鼠的组织中含有大量高分子量的透明质酸。人成纤维细胞分泌高达2 MDa的HA,裸鼹鼠成纤维细胞产生6-12 MDa的HA。这种非常高的HMW-HA (vHMW-HA)在功能上与HMW-HA不同吗?我们发现,与HMW-HA相比,vHMW-HA具有更好的细胞保护特性,并且与CD44受体的相互作用不同,导致不同的转录变化(Takasugi et al. (2020), Nat comm)。这些结果表明vHMW-HA比标准HMW-HA具有更大的治疗效果。
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来源期刊
Cell Stress
Cell Stress Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (miscellaneous)
CiteScore
13.50
自引率
0.00%
发文量
21
审稿时长
15 weeks
期刊介绍: Cell Stress is an open-access, peer-reviewed journal that is dedicated to publishing highly relevant research in the field of cellular pathology. The journal focuses on advancing our understanding of the molecular, mechanistic, phenotypic, and other critical aspects that underpin cellular dysfunction and disease. It specifically aims to foster cell biology research that is applicable to a range of significant human diseases, including neurodegenerative disorders, myopathies, mitochondriopathies, infectious diseases, cancer, and pathological aging. The scope of Cell Stress is broad, welcoming submissions that represent a spectrum of research from fundamental to translational and clinical studies. The journal is a valuable resource for scientists, educators, and policymakers worldwide, as well as for any individual with an interest in cellular pathology. It serves as a platform for the dissemination of research findings that are instrumental in the investigation, classification, diagnosis, and therapeutic management of major diseases. By being open-access, Cell Stress ensures that its content is freely available to a global audience, thereby promoting international scientific collaboration and accelerating the exchange of knowledge within the research community.
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