Reduced Mucin-7 (Muc7) Sialylation and Altered Saliva Rheology in Sjogren's Syndrome Associated Oral Dryness
Reduced Mucin-7 (Muc7) Sialylation and Altered Saliva Rheology in Sjogren's Syndrome Associated Oral Dryness
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DOI：
10.1074/mcp.m115.052993
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发表时间：
2016-03-01
影响因子：
7
通讯作者：
Flowers, Sarah A.
中科院分区：
文献类型：
--
作者：
Chaudhury, Nayab M. A.;Proctor, Gordon B.;Flowers, Sarah A.
干燥综合征是一种慢性自身免疫性疾病，以淋巴细胞渗入和唾液腺、泪腺功能减退为特征。这种唾液功能的丧失会导致口腔干燥、吞咽和言语障碍，并增加感染，并与其他自身免疫性疾病和某些癌症的风险增加有关。尽管存在这种流行疾病的影响，但目前的诊断需要数年时间，部分原因是患者表现的多样性。唾液是一种复杂的生物流体，其主要成分包括高度糖基化的粘蛋白MUC5B和MUC7，这两种粘蛋白具有重要的粘弹性、水化和润滑特性。这项研究调查了Sjogren患者对干燥的感觉(困扰指数问卷)，以及整个口腔唾液和粘膜表面唾液(残留粘膜唾液)的流变学、蛋白质成分和葡聚糖分析，以了解对患者健康影响最大的特性。Sjogren的患者在残留唾液、唾液流率、拉伸流变学、棘皮状(粘稠度)方面表现出统计上的显著降低。虽然患者和对照组的粘蛋白MUC5B和MUC7的浓度相似，但蛋白质免疫印迹和葡聚糖染色的比较发现，Sjogren的粘蛋白糖基化减少，尤其是MUC7。通过消除MUC7释放的O-多糖的LC-MS/MS分析表明，尽管患者的核心1硫酸盐化增加，但唾液酸化的更大程度的减少导致带电多糖的全球下降。这主要是由于具有和不具有岩藻糖基化的扩展的核心2二唾液酸化结构的丢失。MUC7上延伸的岩藻糖化核心2二唾液酸化结构的减少、残留的粘膜湿润度和全口唾液流率似乎对口腔干燥的感觉有负面和累积的影响。观察到的MUC7糖基化变化可能是唾液质量的潜在诊断工具，并可考虑用于这种多因素综合征的未来治疗。
Sjogren's syndrome is a chronic autoimmune disorder characterized by lymphocytic infiltration and hypofunction of salivary and lacrimal glands. This loss of salivary function leads to oral dryness, impaired swallowing and speech, and increased infection and is associated with other autoimmune diseases and an increased risk of certain cancers. Despite the implications of this prevalent disease, diagnosis currently takes years, partly due to the diversity in patient presentation. Saliva is a complicated biological fluid with major constituents, including heavily glycosylated mucins MUC5B and MUC7, important for its viscoelastic and hydrating and lubricating properties. This study investigated Sjogren's patient's perception of dryness (bother index questionnaires) along with the rheological, protein composition, and glycan analysis of whole mouth saliva and the saliva on the mucosal surface (residual mucosal saliva) to understand the properties that most affect patient wellbeing. Sjogren's patients exhibited a statistically significant reduction in residual mucosal saliva, salivary flow rate, and extensional rheology, spinnbarkeit (stringiness). Although the concentration of mucins MUC5B and MUC7 were similar between patients and controls, a comparison of protein Western blotting and glycan staining identified a reduction in mucin glycosylation in Sjogren's, particularly on MUC7. LC-MS/MS analysis of O-glycans released from MUC7 by -elimination revealed that although patients had an increase in core 1 sulfation, the even larger reduction in sialylation resulted in a global decline of charged glycans. This was primarily due to the loss of the extended core 2 disialylated structure, with and without fucosylation. A decrease in the extended, fucosylated core 2 disialylated structure on MUC7, residual mucosal wetness, and whole mouth saliva flow rate appeared to have a negative and cumulative effect on the perception of oral dryness. The observed changes in MUC7 glycosylation could be a potential diagnostic tool for saliva quality and taken into consideration for future therapies for this multifactorial syndrome.