Language

English

Publication Date

1-1-2026

Journal

International Journal of Biological Sciences

DOI

10.7150/ijbs.123875

PMID

41800249

PMCID

PMC12965075

PubMedCentral® Posted Date

1-30-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial pneumonia of unknown etiology. Its pathogenesis involves complex multicellular interactions and signaling pathways, with fibroblast-to-myofibroblast transition (FMT) being critical for fibrogenesis. Although the transcription factor Y-box binding protein 1 (YBX1) regulates processes such as cell proliferation, transcription, translation, and DNA repair, its role in IPF remains undefined. Here, we demonstrate that YBX1 overexpression significantly promotes transforming growth factor-β1 (TGF-β1)-induced pulmonary FMT, leading to substantially increased extracellular matrix (ECM) deposition in primary human (PHLFs) and mouse (PMLFs) lung fibroblasts. Conversely, YBX1 inhibition markedly suppresses TGF-β1-driven aberrant fibroblast migration and activation. Mechanistically, YBX1 interacts with polypyrimidine tract-binding protein 1 (PTBP1) and binds to the protein tyrosine phosphatase nonreceptor type 1 (PTPN1) promoter to transcriptionally regulate PTPN1, thereby driving FMT.

Keywords

Animals, Humans, Y-Box-Binding Protein 1, Mice, Fibroblasts, Lung, Idiopathic Pulmonary Fibrosis, Bleomycin, Transforming Growth Factor beta1, Mice, Inbred C57BL, Transcription Factors, YBX1, YBX1-PTBP1 interaction, PTPN1, fibroblast activation

Published Open-Access

yes

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