Biology of the Heparanase-Heparan Sulfate Axis and Its Role in Disease Pathogenesis.
Biology of the Heparanase-Heparan Sulfate Axis and Its Role in Disease Pathogenesis.
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肝素酶硫酸盐轴的生物学及其在疾病发病机理中的作用。
DOI：
10.1055/s-0041-1725066
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发表时间：
2021-04
影响因子：
5.7
通讯作者：
Ilan, Neta
中科院分区：
文献类型：
--
作者：
Vlodavsky, Israel;Barash, Uri;Nguyen, Hien M.;Yang, Shi-Ming;Ilan, Neta
细胞表面蛋白聚糖是糖萼的重要成分，并参与细胞-细胞和细胞-细胞外基质（ECM）相互作用、酶激活和抑制以及多种信号传导途径，从而调节细胞增殖、存活、粘附、迁移和分化。乙酰肝素酶是哺乳动物硫酸乙酰肝素唯一的降解内切糖苷酶，作为HS蛋白聚糖的“激活剂”，从而调节组织止血。乙酰肝素酶是一种多方面的酶，与硫酸乙酰肝素（主要是syndecan-1）一起通过酶和非酶活性驱动信号转导、免疫细胞活化、外泌体形成、自噬和基因转录。一个重要的特征是乙酰肝素酶刺激多配体蛋白聚糖-1脱落的能力，从而影响其起源细胞的局部和远端的细胞行为。乙酰肝素酶释放HS结合的生长因子、细胞因子和趋化因子的淀粉酶，其被糖萼和ECM中的硫酸乙酰肝素螯合。总的来说，硫酸乙酰肝素-乙酰肝素酶轴在为细胞增殖、分化和功能创造容许环境中起关键作用，通常导致疾病如癌症、炎症、内皮炎、肾功能障碍、组织纤维化和病毒感染的发病机制。
Cell surface proteoglycans are important constituents of the glycocalyx and participate in cell–cell and cell–extracellular matrix (ECM) interactions, enzyme activation and inhibition, and multiple signaling routes, thereby regulating cell proliferation, survival, adhesion, migration, and differentiation. Heparanase, the sole mammalian heparan sulfate degrading endoglycosidase, acts as an “activator” of HS proteoglycans, thus regulating tissue hemostasis. Heparanase is a multifaceted enzyme that together with heparan sulfate, primarily syndecan-1, drives signal transduction, immune cell activation, exosome formation, autophagy, and gene transcription via enzymatic and nonenzymatic activities. An important feature is the ability of heparanase to stimulate syndecan-1 shedding, thereby impacting cell behavior both locally and distally from its cell of origin. Heparanase releases amyriad of HS-bound growth factors, cytokines, and chemokines that are sequestered by heparan sulfate in the glycocalyx and ECM. Collectively, the heparan sulfate–heparanase axis plays pivotal roles in creating a permissive environment for cell proliferation, differentiation, and function, often resulting in the pathogenesis of diseases such as cancer, inflammation, endotheliitis, kidney dysfunction, tissue fibrosis, and viral infection.
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肝素酶的过表达降低了肝素的表达，影响铁稳态并改变对炎症的反应。
影响因子：
3.7
作者：
Asperti M;Stuemler T;Poli M;Gryzik M;Lifshitz L;Meyron-Holtz EG;Vlodavsky I;Arosio P
通讯作者：
Arosio P
影响因子：
20.3
作者：
Axelsson, Jakob;Xu, Ding;Esko, Jeffrey D.
通讯作者：
Esko, Jeffrey D.
影响因子：
3.8
作者：
Bacsa, Sarolta;Karasneh, Ghadah;Shukla, Deepak
通讯作者：
Shukla, Deepak
影响因子：
3.7
作者：
Brockstedt, U;Dobra, K;Hjerpe, A
通讯作者：
Hjerpe, A
影响因子：
4.8
作者：
Brunn, GJ;Bungum, MK;Platt, JL
通讯作者：
Platt, JL