Thrombospondin-2 and extracellular matrix assembly.

Thrombospondin-2 and extracellular matrix assembly.
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DOI:
10.1016/j.bbagen.2014.01.013
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发表时间:
2014-08
影响因子:
3
通讯作者:
Kyriakides, Themis R.
Kyriakides, Themis R.
中科院分区:
生物学3区
文献类型:
--
作者:
Calabro, Nicole E.;Kristofik, Nina J.;Kyriakides, Themis R.

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细胞外基质(ECM)由大量蛋白质和富含亮氨酸的小分子蛋白聚糖(SLRP)组成。在分子水平上理解ECM中单个纤维组分的组装,例如胶原蛋白、弹性蛋白和纤连蛋白。相比之下,ECM中非纤维组分的掺入及其功能尚未完全了解。本文综述了基质细胞蛋白血小板反应蛋白(TSP)2在ECM组装中的作用。基于TSP 2基因缺失小鼠和体外研究的结果,我们描述了TSP 2参与ECM组装、细胞-ECM相互作用和基质金属蛋白酶(MMPs)水平的调节。在这篇综述中总结的证据表明,TSP 2可以影响胶原纤维的形成,而不是纤维的组成部分。改变的ECM组装和ECM的过度分解可以具有积极和消极的后果,包括分别在组织修复期间增加血管生成和损害心脏组织完整性。正确的ECM组装对于维持细胞功能和提供结构支持至关重要。缺乏TSP 2与血管生成增加有关,部分原因是内皮细胞-ECM相互作用改变。因此,ECM组成的微小变化可对细胞和组织功能产生深远影响。本文是特刊“基质介导的细胞行为和特性”的一部分。TSP 2主要作为细胞-ECM相互作用的调节剂起作用,并且可以影响ECM的组装。更重要的是,TSP 2-null ECM增强血管生成反应。因此,可以通过去细胞化技术寻求减少TSP 2并产生新ECM的策略。
Numerous proteins and small leucine-rich proteoglycans (SLRPs) make up the composition of the extracellular matrix (ECM). Assembly of individual fibrillar components in the ECM, such as collagen, elastin, and fibronectin is understood at the molecular level. In contrast, the incorporation of non-fibrillar components and their functions in the ECM are not fully understood. This review will focus on the role of the matricellular protein thrombospondin (TSP) 2 in ECM assembly. Based on findings in TSP2-null mice and in vitro studies, we describe the participation of TSP2 in ECM assembly, cell-ECM interactions, and modulation of the levels of matrix metalloproteinases (MMPs). Evidence summarized in this review suggests that TSP2 can influence collagen fibrillogenesis without being an integral component of fibrils. Altered ECM assembly and excessive breakdown of ECM can have both positive and negative consequences including increased angiogenesis during tissue repair and compromised cardiac tissue integrity, respectively. Proper ECM assembly is critical for maintaining cell functions and providing structural support. Lack of TSP2 is associated with increased angiogenesis, in part, due to altered endothelial cell-ECM interactions. Therefore, minor changes in ECM composition can have profound effects on cell and tissue function. This article is part of a special issue, “Matrix-Mediated Cell Behavior and Properties.” TSP2 functions primarily as a modulator of cell-ECM interactions and can influence the assembly of ECM. More importantly, TSP2-null ECM enhances angiogenic responses. Therefore, strategies can be pursued to reduce TSP2 and generate novel ECM via decellularization techniques.
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