The UIP honeycomb airways are defined by deranged ciliogenesis and elevated mucin biogenesis

ABSTRACT: Honeycombing (HC) is a histological pattern consistent with Usual Interstitial Pneumonia (UIP). HC refers to cystic airways (HC airways) located at sites of dense fibrosis with marked mucus accumulation. Utilizing laser capture microdissection coupled mass spectrometry (LCM-MS), we interrogate the fibrotic HC airway cells and fibrotic uninvolved airway cells (morphologically intact) in 10 UIP specimens; 6 non-fibrotic airway cell specimens served as controls. Furthermore, we perform LCM-MS on the mucus found in 6 UIP and 6 mucinous adenocarcinoma (MA) specimens. The mass spectrometry data were subject to a qualitative and quantitative analysis, and validated by immunohistochemistry. Surprisingly, fibrotic uninvolved and HC airway cells share a similar protein profile, both showing deregulation of SLITs and ROBO pathway as the strongest category. We find that BPIFB1 is the most significantly increased secretome-associated protein in UIP, whereas MUC5AC is the most significantly increased in MA. We conclude that spatial proteomics demonstrates that the fibrotic uninvolved airway cells are abnormal. In addition, fibrotic HC airway cells are enriched in mucin biogenesis proteins and show a marked derangement in proteins essential for ciliogenesis. This unbiased spatial proteomic approach will generate novel and testable hypothesis to decipher fibrosis progression.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung

DISEASE(S): Idiopathic Pulmonary Fibrosis

SUBMITTER: Craig Lawless  

LAB HEAD: Jeremy Herrera

PROVIDER: PXD036465 | Pride | 2025-03-25

REPOSITORIES: Pride