TNF-α-induced NF-κB activation promotes myofibroblast differentiation of LR-MSCs and exacerbates bleomycin-induced pulmonary fibrosis

Jiwei Hou, Tan Ma, Honghui Cao, Yabing Chen, Cong Wang, Xiang Chen, Xiang Zou, Xiaodong Han

Research output: Journal article publicationJournal articleAcademic researchpeer-review

52 Citations (Scopus)


Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and irreversible lung disease of unknown cause. It has been reported that both lung resident mesenchymal stem cells (LR-MSCs) and tumor necrosis factor-α (TNF-α) play important roles in the development of pulmonary fibrosis. However, the underlying connections between LR-MSCs and TNF-α in the pathogenesis of pulmonary fibrosis are still elusive. In this study, we found that the pro-inflammatory cytokine TNF-α and the transcription factor nuclear factor kappa B (NF-κB) p65 subunit were both upregulated in bleomycin-induced fibrotic lung tissue. In addition, we discovered that TNF-α promotes myofibroblast differentiation of LR-MSCs through activating NF-κB signaling. Interestingly, we also found that TNF-α promotes the expression of β-catenin. Moreover, we demonstrated that suppression of the NF-κB signaling could attenuate myofibroblast differentiation of LR-MSCs and bleomycin-induced pulmonary fibrosis which were accompanied with decreased expression of β-catenin. Our data implicates that inhibition of the NF-κB signaling pathway may provide a therapeutic strategy for pulmonary fibrosis, a disease that warrants more effective treatment approaches.
Original languageEnglish
Pages (from-to)2409-2419
Number of pages11
JournalJournal of Cellular Physiology
Issue number3
Publication statusPublished - 1 Mar 2018


  • idiopathic pulmonary fibrosis (IPF)
  • lung resident mesenchymal stem cells (LR-MSCs)
  • myofibroblast differentiation
  • NF-κB signaling
  • tumor necrosis factor-α (TNF-α)

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this