Impaired AMPK control of alveolar epithelial cell metabolism promotes pulmonary fibrosis.

ABSTRACT: Alveolar epithelial type II (AT2) cell dysfunction is implicated in the pathogenesis of familial and sporadic idiopathic pulmonary fibrosis (IPF). We previously demonstrated that expression of an AT2 cell-exclusive disease-associated protein isoform (SP-CI73T) in murine and patient-specific induced pluripotent stem cell-derived (iPSC-derived) AT2 cells leads to a block in late macroautophagy and promotes time-dependent mitochondrial impairments; however, how a metabolically dysfunctional AT2 cell results in fibrosis remains elusive. Here, using murine and human iPSC-derived AT2 cell models expressing SP-CI73T, we characterize the molecular mechanisms governing alterations in AT2 cell metabolism that lead to increased glycolysis, decreased mitochondrial biogenesis, disrupted fatty acid oxid

SUBMITTER: Rodriguez LR 

PROVIDER: S-EPMC12333953 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature