Chop deficiency protects mice against bleomycin-induced pulmonary fibrosis by attenuating M2 macrophage production

Yingying Yao, Yi Wang, Zhijun Zhang, Long He, Jianghui Zhu, Meng Zhang, Xiaoyu He, Zhenshun Cheng, Qilin Ao, Yong Cao, Ping Yang, Yunchao Su, Jianping Zhao, Shu Zhang, Qilin Yu, Qin Ning, Xudong Xiang, Weining Xiong, Cong Yi Wang, Yongjian Xu

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

C/EBP homologous protein (Chop) has been shown to have altered expression in patients with idiopathic pulmonary fibrosis (IPF), but its exact role in IPF pathoaetiology has not been fully addressed. Studies conducted in patients with IPF and Chop -/- mice have dissected the role of Chop and endoplasmic reticulum (ER) stress in pulmonary fibrosis pathogenesis. The effect of Chop deficiency on macrophage polarization and related signalling pathways were investigated to identify the underlying mechanisms. Patients with IPF and mice with bleomycin (BLM)-induced pulmonary fibrosis were affected by the altered Chop expression and ER stress. In particular, Chop deficiency protected mice against BLM-induced lung injury and fibrosis. Loss of Chop significantly attenuated transforming growth factor β (TGF-β) production and reduced M2 macrophage infiltration in the lung following BLM induction. Mechanistic studies showed that Chop deficiency repressed the M2 program in macrophages, which then attenuated TGF-β secretion. Specifically, loss of Chop promoted the expression of suppressors of cytokine signaling 1 and suppressors of cytokine signaling 3, and through which Chop deficiency repressed signal transducer and activator of transcription 6/peroxisome proliferator-activated receptor gamma signaling, the essential pathway for the M2 program in macrophages. Together, our data support the idea that Chop and ER stress are implicated in IPF pathoaetiology, involving at least the induction and differentiation of M2 macrophages.

Original languageEnglish (US)
Pages (from-to)915-925
Number of pages11
JournalMolecular Therapy
Volume24
Issue number5
DOIs
StatePublished - May 1 2016

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Transcription Factor CHOP
Protein Deficiency
Pulmonary Fibrosis
Bleomycin
Macrophages
Idiopathic Pulmonary Fibrosis
Endoplasmic Reticulum Stress
Transforming Growth Factors
STAT6 Transcription Factor
Cytokines
PPAR gamma
Lung Injury

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Cite this

Chop deficiency protects mice against bleomycin-induced pulmonary fibrosis by attenuating M2 macrophage production. / Yao, Yingying; Wang, Yi; Zhang, Zhijun; He, Long; Zhu, Jianghui; Zhang, Meng; He, Xiaoyu; Cheng, Zhenshun; Ao, Qilin; Cao, Yong; Yang, Ping; Su, Yunchao; Zhao, Jianping; Zhang, Shu; Yu, Qilin; Ning, Qin; Xiang, Xudong; Xiong, Weining; Wang, Cong Yi; Xu, Yongjian.

In: Molecular Therapy, Vol. 24, No. 5, 01.05.2016, p. 915-925.

Research output: Contribution to journalArticle

Yao, Y, Wang, Y, Zhang, Z, He, L, Zhu, J, Zhang, M, He, X, Cheng, Z, Ao, Q, Cao, Y, Yang, P, Su, Y, Zhao, J, Zhang, S, Yu, Q, Ning, Q, Xiang, X, Xiong, W, Wang, CY & Xu, Y 2016, 'Chop deficiency protects mice against bleomycin-induced pulmonary fibrosis by attenuating M2 macrophage production', Molecular Therapy, vol. 24, no. 5, pp. 915-925. https://doi.org/10.1038/mt.2016.36
Yao, Yingying ; Wang, Yi ; Zhang, Zhijun ; He, Long ; Zhu, Jianghui ; Zhang, Meng ; He, Xiaoyu ; Cheng, Zhenshun ; Ao, Qilin ; Cao, Yong ; Yang, Ping ; Su, Yunchao ; Zhao, Jianping ; Zhang, Shu ; Yu, Qilin ; Ning, Qin ; Xiang, Xudong ; Xiong, Weining ; Wang, Cong Yi ; Xu, Yongjian. / Chop deficiency protects mice against bleomycin-induced pulmonary fibrosis by attenuating M2 macrophage production. In: Molecular Therapy. 2016 ; Vol. 24, No. 5. pp. 915-925.
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AU - He, Xiaoyu

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AU - Su, Yunchao

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AU - Yu, Qilin

AU - Ning, Qin

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