Quantitative proteomics reveals the mechanism of endoplasmic reticulum stress-mediated pulmonary fibrosis in mice.

Pulmonary fibrosis is a progressive disease that can lead to respiratory failure. Many types of cells are involved in the progression of pulmonary fibrosis. This study utilized quantitative proteomics to investigate the mechanism of TGF-β-induced fibrosis-like changes in mouse epithelial cells. Our findings revealed that TGF-β significantly impacted biological processes related to the endoplasmic reticulum, mitochondrion, and ribonucleoprotein complex. Pull-down assay coupled with proteomics identified 114 proteins that may directly interact with TGF-β, and their functions were related to mitochondria, translation, ubiquitin ligase conjugation, mRNA processing, and actin binding. Among them, 17 molecules were also found in different expression proteins (DEPs) of quantitative proteomic, such as H1F0, MED21, SDF2L1, DAD1, and TMX1. Additionally, TGF-β decreased the folded structure and the number of ribosomes in the endoplasmic reticulum and increased the expression of key proteins in the unfolded protein response, including HRD1, PERK, and ERN1. Overall, our study suggested that TGF-β induced fibrotic changes in mouse lung epithelial cells by ER stress and initiated the unfolded protein response through the PRKCSH/IRE1 and PERK/GADD34/CHOP signaling pathways.