Ectopic Expression of <i>MUC5B</i> in the Respiratory Bronchiole Initiates Endoplasmic Reticulum Stress in the IPF Lung.

ABSTRACT: We used spatial transcriptomics from idiopathic pulmonary fibrosis (IPF) and unaffected control lung tissue to further understand the pathogenesis of MUC5B-driven lung fibrosis. We captured 43 fields of view in 15 IPF and 13 controls with and without the MUC5B promoter variant using the CosMx^® platform and identified 19 cell types via semi-supervised clustering. MUC5B was ectopically expressed in AT2 cells in controls with the risk variant. We observed a decreased proportion of AT2 cells in controls and an increased proportion of aberrant basaloid cells in IPF associated with the MUC5B risk variant. We identified co-localized expression of MUC5B in respiratory bronchioles with 13 genes including the endoplasmic reticulum (ER) stress marker XBP1

SUBMITTER: Blumhagen RZ 

PROVIDER: S-EPMC12834077 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature