Targeting USP11 counteracts <i>SFTPC^I73T</i> -associated interstitial lung disease in hiPSCs-derived alveolar organoids and in vivo models.

ABSTRACT: Background: Interstitial lung disease (ILD) is a pulmonary disorder characterized by a combination of inflammation and fibrosis in the lung parenchyma, which initiates with the dysfunction of alveolar epithelial cells (AECs). The alveolar cells secrete surfactant proteins that lowers the surface tension of fluids in the lungs and maintains the stability of pulmonary tissue. Mutations on surfactant protein C (SFTPC), particularly I73T, are associated with a toxic gain of function that causes misfolding and the accumulation of immature SFTPC proteins, triggering pulmonary fibrosis (PF). Therefore, it is crucial to block the accumulation of the SFTPC ^I73T protein during ILD progression. Methods: We used a loss-of-function-based CRISPR/Cas9 library kit to screen

SUBMITTER: Karapurkar JK 

PROVIDER: S-EPMC11984411 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature