Distinct effects of different matrix proteoglycans on collagen fibrillogenesis and cell-mediated collagen reorganization.

Distinct effects of different matrix proteoglycans on collagen fibrillogenesis and cell-mediated collagen reorganization.
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不同基质蛋白聚糖对胶原纤维形成和细胞介导的胶原重组的不同影响。

DOI:
10.1038/s41598-020-76107-0
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发表时间:
2020-11-04
期刊:
影响因子:
4.6
通讯作者:
Wells RG
Wells RG
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chen D;Smith LR;Khandekar G;Patel P;Yu CK;Zhang K;Chen CS;Han L;Wells RG

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细胞外基质(ECM)是由纤维性胶原蛋白以及额外的蛋白质和碳水化合物组成的复杂混合物。蛋白多糖(PG)是细胞外基质异质性的重要来源,在细胞外基质的结构和功能中起重要作用。富含亮氨酸的小分子蛋白多糖(SLRPs)作为胶原纤维形成和组织的介质已被广泛研究,但大基质PGs在胶原基质中的作用却鲜为人知。在这项研究中,我们发现不同的基质PG在调节胶原行为方面有不同的作用。我们发现Verscan,一种大的硫酸软骨素PG,在浊度实验中促进胶原纤维形成,并上调细胞介导的胶原致密和重组,而aggrecan,一种结构相似的大PG,对胶原有不同的,往往是相反的作用。与弗西肯相比,核心蛋白聚糖和鲁米肯在调节胶原蛋白行为方面也具有不同的功能。基质前列腺素与胶原相互作用的不同方式对于理解细胞外基质在纤维化和癌症等疾病中的作用具有重要意义,并提示基质前列腺素是潜在的治疗靶点。
The extracellular matrix (ECM) is a complex mixture composed of fibrillar collagens as well as additional protein and carbohydrate components. Proteoglycans (PGs) contribute to the heterogeneity of the ECM and play an important role in its structure and function. While the small leucine rich proteoglycans (SLRPs), including decorin and lumican, have been studied extensively as mediators of collagen fibrillogenesis and organization, the function of large matrix PGs in collagen matrices is less well known. In this study, we showed that different matrix PGs have distinct roles in regulating collagen behaviors. We found that versican, a large chondroitin sulfate PG, promotes collagen fibrillogenesis in a turbidity assay and upregulates cell-mediated collagen compaction and reorganization, whereas aggrecan, a structurally-similar large PG, has different and often opposing effects on collagen. Compared to versican, decorin and lumican also have distinct functions in regulating collagen behaviors. The different ways in which matrix PGs interact with collagen have important implications for understanding the role of the ECM in diseases such as fibrosis and cancer, and suggest that matrix PGs are potential therapeutic targets.
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