NLRP3 inflammasome activation in alveolar epithelial cells promotes myofibroblast differentiation of lung-resident mesenchymal stem cells during pulmonary fibrogenesis

Jie Ji, Jiwei Hou, Yunhui Xia, Zou Xiang, Xiaodong Han

Research output: Journal article publicationJournal articleAcademic researchpeer-review

1 Citation (Scopus)

Abstract

Idiopathic pulmonary fibrosis (IPF) is a lethal and agnogenic interstitial lung disease, which has limited therapeutic options. Recently, the NOD-, LRR- and pyrin domain-containing 3 (NLRP3) inflammasome has been demonstrated as an important contributor to various fibrotic diseases following its persistent activation. However, the role of NLRP3 inflammasome in pulmonary fibrogenesis still needs to be further clarified. Here, we found that the activation of the NLRP3 inflammasome was raised in fibrotic lungs. In addition, the NLRP3 inflammasome was found to be activated in alveolar epithelial cells (AECs) in the lung tissue of both IPF patients and pulmonary fibrosis mouse models. Further research revealed that epithelial cells, following activation of the NLRP3 inflammasome, could induce the myofibroblast differentiation of lung-resident mesenchymal stem cells (LR-MSCs). In addition, inhibiting the activation of the NLRP3 inflammasome in epithelial cells promoted the expression of dickkopf-1 (DKK1), a secreted Wnt antagonist. DKK1 was capable of suppressing the profibrogenic differentiation of LR-MSCs and bleomycin-induced pulmonary fibrosis. In conclusion, this study not only provides a further in-depth understanding of the pathogenesis of pulmonary fibrosis, but also reveals a potential therapeutic strategy for disorders associated with pulmonary fibrosis.

Original languageEnglish
Article number166077
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1867
Issue number5
DOIs
Publication statusPublished - 1 May 2021

Keywords

  • Alveolar epithelial cell (AEC) dysfunction
  • Dickkopf-1 (DKK1)
  • Lung-resident mesenchymal stem cells (LR-MSCs)
  • NLRP3 inflammasome
  • Pulmonary fibrosis
  • Wnt/β-catenin

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

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