Developmental Glycobiology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892-4370, USA.
Division of Intramural Research, NIEHS, National Institutes of Health, Research Triangle Park, Durham, NC 27514, USA.
Glycobiology. 2023 Jun 21;33(6):476-489. doi: 10.1093/glycob/cwad031.
The COVID-19 global pandemic has underscored the need to understand how viruses and other pathogens are able to infect and replicate within the respiratory system. Recent studies have highlighted the role of highly O-glycosylated mucins in the protection of the respiratory system as well as how mucin-type O-glycosylation may be able to modify viral infectivity. Therefore, we set out to identify the specific genes controlling mucin-type O-glycosylation throughout the mouse respiratory system as well as determine how their expression and the expression of respiratory mucins is influenced by infection or injury. Here, we show that certain mucins and members of the Galnt family are abundantly expressed in specific respiratory tissues/cells and demonstrate unique patterns of O-glycosylation across diverse respiratory tissues. Moreover, we find that the expression of certain Galnts and mucins is altered during lung infection and injury in experimental mice challenged with infectious agents, toxins, and allergens. Finally, we examine gene expression changes of Galnts and mucins in a mouse model of SARS-CoV-2 infection. Our work provides foundational knowledge regarding the specific expression of Galnt enzyme family members and mucins throughout the respiratory system, and how their expression is altered upon lung infection and injury.
新型冠状病毒全球大流行凸显了人们需要了解病毒和其他病原体如何在呼吸系统中感染和复制。最近的研究强调了高度 O-糖基化粘蛋白在保护呼吸系统中的作用，以及粘蛋白型 O-糖基化如何能够改变病毒的感染力。因此，我们着手确定控制整个小鼠呼吸系统中粘蛋白型 O-糖基化的特定基因，并确定其表达以及呼吸粘蛋白的表达如何受到感染或损伤的影响。在这里，我们表明某些粘蛋白和 Galnt 家族成员在特定的呼吸道组织/细胞中大量表达，并在不同的呼吸道组织中表现出独特的 O-糖基化模式。此外，我们发现某些 Galnts 和粘蛋白的表达在实验小鼠受到感染性物质、毒素和过敏原挑战时的肺部感染和损伤期间发生改变。最后，我们在 SARS-CoV-2 感染的小鼠模型中检查 Galnts 和粘蛋白的基因表达变化。我们的工作提供了关于 Galnt 酶家族成员和粘蛋白在整个呼吸系统中的特定表达以及它们在肺部感染和损伤时的表达如何改变的基础知识。
