Loss of core-fucosylation of SPARC impairs collagen binding and contributes to COPD.

ABSTRACT: Chronic obstructive pulmonary disease (COPD) is a progressive lung disease with high morbidity and mortality worldwide. Although several mechanisms to account for deleterious immune effects were proposed, molecular description for the underlying alveolar structural alterations for COPD is lacking. Here, silencing of α1,6-fucosyltransferase (Fut8), the enzyme for core-fucosylation and highly expressed in lung stem cells, resulted in alveolar structural changes in lung organoids, recapitulating COPD. Site-specific mass spectrometry analysis demonstrated that the secreted protein acidic and rich in cysteine (SPARC), which binds collagen, contains a core-fucosylation site in its VCSNDN^cfK glycopeptide. Biacore assay showed markedly reduced collagen binding of SPARC lacking core fuco

SUBMITTER: Wu TJ 

PROVIDER: S-EPMC9174126 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature