Language
English
Publication Date
8-2-2025
Journal
Nature Communications
DOI
10.1038/s41467-025-61795-x
PMID
40753090
PMCID
PMC12318044
PubMedCentral® Posted Date
8-2-2025
PubMedCentral® Full Text Version
Post-print
Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal disease characterized by excessive extracellular matrix deposition. Current IPF therapies slow disease progression but do not stop or reverse it. The (myo)fibroblasts are thought to be the main cellular contributors to excessive extracellular matrix production in IPF. Here we show that fibrotic alveolar type II cells regulate production and crosslinking of extracellular matrix via the co-transcriptional activator YAP. YAP leads to increased expression of Lysl oxidase (LOX) and subsequent LOX-mediated crosslinking by fibrotic alveolar type II cells. Pharmacological YAP inhibition via verteporfin reverses fibrotic alveolar type II cell reprogramming and LOX expression in experimental lung fibrosis in vivo and in human fibrotic tissue ex vivo. We thus identify YAP-TEAD/LOX inhibition in alveolar type II cells as a promising potential therapy for IPF patients.
Keywords
Humans, Animals, Idiopathic Pulmonary Fibrosis, YAP-Signaling Proteins, Protein-Lysine 6-Oxidase, Signal Transduction, Verteporfin, Transcription Factors, Adaptor Proteins, Signal Transducing, Mice, Alveolar Epithelial Cells, Disease Models, Animal, Extracellular Matrix, Male, Lung, Mice, Inbred C57BL, DNA-Binding Proteins, Female, Cell Cycle Proteins, Translational research, Molecular medicine, Target identification, Next-generation sequencing
Published Open-Access
yes
Recommended Citation
Wagner, Darcy Elizabeth; Alsafadi, Hani N; Mitash, Nilay; et al., "Inhibition of Epithelial Cell Yap-Tead/Lox Signaling Attenuates Pulmonary Fibrosis in Preclinical Models" (2025). Faculty, Staff and Students Publications. 6786.
https://digitalcommons.library.tmc.edu/baylor_docs/6786