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  2. M2 macrophages promote myofibroblast differentiation of LR-MSCs and are associated with pulmonary fibrogenesis

M2 macrophages promote myofibroblast differentiation of LR-MSCs and are associated with pulmonary fibrogenesis

  • Cell Commun Signal. 2018 Nov 23;16(1):89. doi: 10.1186/s12964-018-0300-8.
Jiwei Hou 1 2 Jingyan Shi 1 2 Ling Chen 1 2 Zhongyang Lv 1 2 Xiang Chen 1 2 Honghui Cao 1 2 Zou Xiang 3 Xiaodong Han 4 5
Affiliations

Affiliations

  • 1 Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Hankou Road 22, Nanjing, 210093, China.
  • 2 Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, 210093, China.
  • 3 Department of Health Technology and Informatics, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China.
  • 4 Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Hankou Road 22, Nanjing, 210093, China. hanxd@nju.edu.cn.
  • 5 Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, 210093, China. hanxd@nju.edu.cn.
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.

Keywords

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

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