Reduced Sialylation of Airway Mucin Impairs Mucus Transport by Altering the Biophysical Properties of Mucin
Elex S. Harris, Hannah J. McIntire, Marina Mazur, Hinnerk Schulz-Hildebrandt, Hui Min Leung, Guillermo J Tearney, Stefanie Krick, Steven M. Rowe, Jarrod W. Barnes
TL;DR
Reduced sialylation of airway mucin impairs mucus transport by changing mucin properties, which could be a target for treating diseases like cystic fibrosis.
Contribution
This study shows that reduced sialylation of MUC5B directly impairs mucociliary transport and identifies ST3Gal1 as a potential therapeutic target.
Findings
Reduced sialylation leads to a lower charged MUC5B form and decreased polymer expansion.
Blocking α−2,3 sialylation impairs mucociliary transport in human and rat airways.
ST3Gal1 expression is downregulated in cystic fibrosis and partially restored by CFTR correction.
Abstract
Mucus stasis is a pathologic hallmark of muco-obstructive diseases, including cystic fibrosis (CF). Mucins, the principal component of mucus, are extensively modified with hydroxyl (O)-linked glycans, which are largely terminated by sialic acid. Sialic acid is a negatively charged monosaccharide and contributes to the biochemical/biophysical properties of mucins. Reports suggest that mucin sialylation may be altered in CF; however, the consequences of reduced sialylation on mucus clearance have not been fully determined. Here, we investigated the consequences of reduced sialylation on the charge state and conformation of the most prominent airway mucin, MUC5B, and defined the functional consequences of reduced sialylation on mucociliary transport (MCT). Reduced sialylation contributed to a lower charged MUC5B form and decreased polymer expansion. The inhibition of total mucin…
Genes, proteins, chemicals, diseases, species, mutations and cell lines named across the full text — each resolved to its canonical identifier and authoritative record.
Click any figure to enlarge with its caption.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8Peer Reviews
No public reviews on file for this paper yet. If you reviewed it on a platform where reviews are public (OpenReview, ICLR, NeurIPS, ICML), you can paste yours below so the community can read it here.
Videos
No videos yet. Explain this paper in a talk, walkthrough, or lecture? Add one.
Taxonomy
TopicsCystic Fibrosis Research Advances · Glycosylation and Glycoproteins Research · Carbohydrate Chemistry and Synthesis