M2 macrophages promote myofibroblast differentiation of LR-MSCs and are associated with pulmonary fibrogenesis 11 Medical and Health Sciences 1102 Cardiorespiratory Medicine and Haematology

Jiwei Hou, Jingyan Shi, Ling Chen, Zhongyang Lv, Xiang Chen, Honghui Cao, Zou Xiang, Xiaodong Han

Research output: Journal article publicationJournal articleAcademic researchpeer-review

26 Citations (Scopus)

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by the histopathological pattern of usual interstitial pneumonia and is associated with a high mortality rate. Recently, lung resident mesenchymal stem cells (LR-MSCs) have been identified as an important contributor to myofibroblast activation in pulmonary fibrosis. Macrophages are also believed to play a critical role in pulmonary fibrosis. However, the underlying connections between LR-MSCs and macrophages in the pathogenesis of pulmonary fibrosis are still elusive. Methods: In this study, we investigated the interaction between LR-MSCs and macrophages using a bleomycin-induced mouse pulmonary fibrosis model and a coculture system. Results: Here, we show that blocking pulmonary macrophage infiltration attenuated bleomycin-induced pulmonary fibrosis. In addition, as determined by flow cytometry, we discovered that the recruited macrophages in fibrotic lungs of bleomycin-treated mice were mainly M2 macrophages. In particular, we found that M2, rather than M1 macrophages, promoted myofibroblast differentiation of LR-MSCs. Moreover, we demonstrated that suppression of the Wnt/β-catenin signaling pathway could attenuate myofibroblast differentiation of LR-MSCs induced by M2 macrophages and bleomycin-induced pulmonary fibrosis. Tissue samples from IPF patients confirmed the infiltration of M2 macrophages and activation of Wnt/β-catenin signaling pathway. Conclusion: In summary, this study furthered our understanding of the pulmonary fibrosis pathogenesis and highlighted M2 macrophages as a critical target for treating pulmonary fibrosis.

Original languageEnglish
Article number89
JournalCell Communication and Signaling
Volume16
Issue number1
DOIs
Publication statusPublished - 23 Nov 2018

Keywords

  • Idiopathic pulmonary fibrosis (IPF)
  • Lung resident mesenchymal stem cells (LR-MSCs)
  • M2 macrophages
  • Myofibroblast differentiation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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