Abstract:
Dupuytren\'s disease (DD) is a prevalent fibroproliferative disorder of the hand, shaped by genetic, epigenetic, and environmental influences. The extracellular matrix (ECM) is a complex assembly of diverse macromolecules. Alterations in the ECM\'s content, structure and organization can impact both normal physiological functions and pathological conditions. This study explored the content and organization of glycosaminoglycans, proteoglycans, and collagen in the ECM of patients at various stages of DD, assessing their potential as prognostic indicators. This research reveals, for the first time, relevant changes in the complexity of chondroitin/dermatan sulfate structures, specifically an increase of disaccharides containing iduronic acid residues covalently linked to either N-acetylgalactosamine 6-O-sulfated or N-acetylgalactosamine 4-O-sulfated, correlating with the disease\'s severity. Additionally, we noted an increase in versican expression, a high molecular weight proteoglycan, across stages I to IV, while decorin, a small leucine-rich proteoglycan, significantly diminishes as DD progresses, both confirmed by mRNA analysis and protein detection via confocal microscopy. Coherent anti-Stokes Raman scattering (CARS) microscopy further demonstrated that collagen fibril architecture in DD varies importantly with disease stages. Moreover, the urinary excretion of both hyaluronic and sulfated glycosaminoglycans markedly decreased among DD patients.Our findings indicate that specific proteoglycans with galactosaminoglycan chains and collagen arrangements could serve as biomarkers for DD progression. The reduction in glycosaminoglycan excretion suggests a systemic manifestation of the disease.
摘要:
Dupuytren病(DD)是一种常见的手部纤维增生性疾病,由基因塑造,表观遗传,和环境影响。细胞外基质(ECM)是多种大分子的复杂组装体。ECM内容的更改,结构和组织可以影响正常的生理功能和病理状况。本研究探讨了糖胺聚糖的含量和组织,蛋白聚糖,和不同阶段患者ECM中的胶原蛋白,评估其作为预后指标的潜力。这项研究揭示,第一次,软骨素/硫酸皮肤素结构复杂性的相关变化,特别是含有与N-乙酰半乳糖胺6-O-硫酸化或N-乙酰半乳糖胺4-O-硫酸化共价连接的艾杜糖醛酸残基的二糖的增加,与疾病的严重程度有关。此外,我们注意到versican表达的增加,一种高分子量的蛋白多糖,跨越阶段I到阶段IV,当装饰素的时候,一种富含亮氨酸的蛋白多糖,随着DD的进展显着减少,通过共聚焦显微镜的mRNA分析和蛋白质检测证实。相干反斯托克斯拉曼散射(CARS)显微镜进一步证明,DD中的胶原蛋白原纤维结构随疾病分期而变化。此外,DD患者的尿中透明质酸和硫酸化糖胺聚糖的排泄量均显著降低.我们的发现表明,具有半乳糖胺聚糖链和胶原蛋白排列的特定蛋白聚糖可以作为DD进展的生物标志物。糖胺聚糖排泄的减少提示该疾病的全身性表现。