Aberrant intermediate alveolar epithelial cells promote pathogenic activation of lung fibroblasts in preclinical fibrosis models.

ABSTRACT: Pulmonary fibrosis (PF) is a progressive disease histologically defined by pathological fibroblasts and epithelial cells. PF lungs contain alveolar type 2 epithelial cells (AT2s) that acquire an aberrant intermediate state phenotype. However, the direct role of these cells in PF and the signals causing them to arise and persist are not fully known. To address this, we harness the Sftpc^C121G mouse model, where expression of a PF-associated mutation in the AT2-specific surfactant protein C (Sftpc) gene results in AT2 dysfunction and spontaneous lung fibrosis. Here, we identify aberrant intermediate epithelial cells in Sftpc^C121G lungs that share transcriptional profiles with human PF aberrant basaloid cells and develop a profibrotic interactome with fibroblasts. We deve

SUBMITTER: Hoffman ET 

PROVIDER: S-EPMC12484947 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature