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核心蛋白聚糖:一种新兴的小富含亮氨酸的蛋白聚糖 (SLRP) 标志物及其临床病理意义。

Biglycan: an emerging small leucine-rich proteoglycan (SLRP) marker and its clinicopathological significance.

机构信息

Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, 110 029, India.

Government Medical College, Kozhikode, Kerala, India.

出版信息

Mol Cell Biochem. 2021 Nov;476(11):3935-3950. doi: 10.1007/s11010-021-04216-z. Epub 2021 Jun 28.

Abstract

Extracellular matrix (ECM) plays an important role in the structural organization of tissue and delivery of external cues to the cell. Biglycan, a class I small leucine-rich proteoglycans (SLRP), is a key component of the ECM that participates in scaffolding the collagen fibrils and mediates cell signaling. Dysregulation of biglycan expression can result in wide range of clinical conditions such as metabolic disorder, inflammatory disorder, musculoskeletal defects and malignancies. In this review, we aim to update our current understanding regarding the link between altered expression of biglycan and different clinicopathological states. Biglycan interacts with toll like receptors (TLR)-2 and TLR-4 on the immune cells which initiates inflammation and aggravates inflammatory disorders. ECM unbound soluble biglycan acts as a DAMP (danger associated molecular pattern) resulting in sterile inflammation. Dysregulation of biglycan expression is also observed in inflammatory metabolic conditions such as atherosclerosis and obesity. In cancer, high-biglycan expression facilitates tumor growth, invasion and metastasis which is associated with poor clinical outcome. As a pivotal structural component of the ECM, biglycan strengthens the musculoskeletal system and its absence is associated with musculoskeletal defects. Thus, SLRP biglycan is a potential marker which is significantly altered in different clinicopathological states.

摘要

细胞外基质 (ECM) 在组织的结构组织和向细胞传递外部线索方面起着重要作用。核心蛋白聚糖 (Biglycan) 是细胞外基质的主要成分之一,属于 I 型小富含亮氨酸的蛋白聚糖 (SLRP),参与了胶原纤维的支架形成,并介导细胞信号转导。Biglycan 的表达失调可导致多种临床病症,如代谢紊乱、炎症性疾病、肌肉骨骼缺陷和恶性肿瘤。在本综述中,我们旨在更新对 Biglycan 表达改变与不同临床病理状态之间联系的认识。Biglycan 与免疫细胞上的 Toll 样受体 (TLR)-2 和 TLR-4 相互作用,引发炎症并加重炎症性疾病。未与细胞外基质结合的可溶性 Biglycan 作为 DAMP(危险相关分子模式),导致无菌性炎症。Biglycan 的表达失调也存在于炎症代谢疾病中,如动脉粥样硬化和肥胖症。在癌症中,高表达 Biglycan 促进肿瘤生长、侵袭和转移,与不良的临床结局相关。作为细胞外基质的关键结构成分,Biglycan 增强了肌肉骨骼系统,其缺失与肌肉骨骼缺陷相关。因此,SLRP Biglycan 是一种潜在的标志物,在不同的临床病理状态下显著改变。

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