INSERM UMR1193, Paris-Saclay University, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément, 92220 Châtenay-Malabry, France.
INSERM UMR1163, French Reference Center for Skeletal Dysplasia, Imagine Institute, Paris University, 24 Boulevard du Montparnasse, 75015 Paris, France.
Genes (Basel). 2021 Oct 20;12(11):1654. doi: 10.3390/genes12111654.
Proteoglycans consist of proteins linked to sulfated glycosaminoglycan chains. They constitute a family of macromolecules mainly involved in the architecture of organs and tissues as major components of extracellular matrices. Some proteoglycans also act as signaling molecules involved in inflammatory response as well as cell proliferation, adhesion, and differentiation. Inborn errors of proteoglycan metabolism are a group of orphan diseases with severe and irreversible skeletal abnormalities associated with multiorgan impairments. Identifying the gene variants that cause these pathologies proves to be difficult because of unspecific clinical symptoms, hardly accessible functional laboratory tests, and a lack of convenient blood biomarkers. In this review, we summarize the molecular pathways of proteoglycan biosynthesis, the associated inherited syndromes, and the related biochemical screening techniques, and we focus especially on a circulating proteoglycan called bikunin and on its potential as a new biomarker of these diseases.
蛋白聚糖由与硫酸化糖胺聚糖链连接的蛋白质组成。它们构成了一大类大分子，主要参与器官和组织的结构，作为细胞外基质的主要成分。一些蛋白聚糖也作为信号分子发挥作用，参与炎症反应以及细胞增殖、黏附和分化。蛋白聚糖代谢的先天性缺陷是一组孤儿病，伴有严重和不可逆转的骨骼异常，并伴有多器官损伤。由于临床表现不特异、功能实验室检测难以获得以及缺乏方便的血液生物标志物，因此确定导致这些病理的基因突变证明是困难的。在这篇综述中，我们总结了蛋白聚糖生物合成的分子途径、相关的遗传性综合征以及相关的生化筛选技术，我们特别关注一种称为 bikunin 的循环蛋白聚糖及其作为这些疾病的新型生物标志物的潜力。
