Syndecans in chronic inflammatory and autoimmune diseases: Pathological insights and therapeutic opportunities.
Syndecans in chronic inflammatory and autoimmune diseases: Pathological insights and therapeutic opportunities.
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DOI：
10.1002/jcp.26388
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发表时间：
2018-09
影响因子：
5.6
通讯作者：
Ahmed S
中科院分区：
文献类型：
--
作者：
Agere SA;Kim EY;Akhtar N;Ahmed S
多配体聚糖（Syndecans，SDC）是硫酸乙酰肝素蛋白聚糖（heparan sulfate proteoglycans，HSPG）糖蛋白家族，广泛表达于所有哺乳动物组织的细胞表面和细胞外基质。有四种哺乳动物多配体蛋白聚糖，SDC-1至4，其通过独立的和生长因子介导的信号传导在细胞粘附、迁移、增殖、分化和血管生成中发挥关键作用。SDC的表达改变通常在自身免疫性疾病、癌症、HIV感染和许多其他病理状况中观察到。SDC通过与多种配体、受体和其他蛋白质（包括细胞外基质、糖蛋白、整联蛋白、形态发生素和各种生长因子和趋化因子以及它们的受体和激酶沿着）相互作用来调节疾病进展。具体而言，存在于细胞表面的SDC可以直接结合趋化因子以增强其与受体的结合、下游信号传导和迁移。或者，SDC可以被切割和脱落以介导趋化因子和生长因子信号传导途径的负调节和配体螯合。重要的是，SDC脱落可能是炎症的生物标志物，特别是在慢性炎症性疾病中。虽然目前癌症和几种自身免疫性疾病的治疗方法已经彻底改变了治疗结果，但了解SDC的病理生理作用以及HSPG模拟物或拮抗剂对细胞因子信号传导网络的使用可能会发现潜在的新型靶向治疗方法。本文主要综述了SDC在疾病过程中的作用、SDC介导其生物学功能的机制以及靶向SDC作为未来潜在治疗方法的可能性。
Syndecans (SDCs) are a family of heparan sulfate proteoglycans (HSPGs) glycoproteins ubiquitously expressed on the cell surfaces and extracellular matrix of all mammalian tissues. There are four mammalian syndecans, SDC-1 thorough 4, which play a critical role in cell adhesion, migration, proliferation, differentiation, and angiogenesis through independent and growth factor mediated signaling. An altered expression of SDCs is often observed in autoimmune disorders, cancer, HIV infection, and many other pathological conditions. SDCs modulate disease progression by interacting with a diverse array of ligands, receptors, and other proteins, including extracellular matrix, glycoproteins, integrins, morphogens, and various growth factors and chemokines, along with their receptors and kinases. Specifically, SDCs present on cell surface can bind directly to chemokines to enhance their binding to receptors, downstream signaling, and migration. Alternatively, SDCs can be cleaved and shed to mediate negative regulation of chemokine and growth factor signaling pathways and ligand sequestration. Importantly, SDC shedding may be a biomarker of inflammation, especially in chronic inflammatory diseases. While the current therapies for cancer and several autoimmune disorders have revolutionized treatment outcomes, understanding the pathophysiological role of SDCs and the use of HSPG mimetic or antagonists on cytokine signaling networks may uncover potentially novel targeted therapeutic approaches. This review mainly summarizes the current findings on the role of individual SDCs in disease processes, mechanisms through which SDCs mediate their biological functions, and the possibility of targeting SDCs as future potential therapeutic approaches.
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