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Molecular Medicine

, Volume 18, Issue 6, pp 992–1002 | Cite as

Inhibition of α-SMA by the Ectodomain of FGFR2c Attenuates Lung Fibrosis

  • Wang Ju
  • Yu Zhihong
  • Zhou Zhiyou
  • Huang Qin
  • Wang Dingding
  • Sun Li
  • Zhu Baowei
  • Wei Xing
  • He Ying
  • Hong An
Research Article

Abstract

The soluble ectodomain of fibroblast growth factor receptor-IIIc (sFGFR2c) is able to bind to fibroblast growth factor (FGF) ligands and block the activation of the FGF-signaling pathway. In this study, sFGFR2c inhibited lung fibrosis dramatically in vitro and in vivo. The upregulation of α-smooth muscle actin (α-SMA) in fibroblasts by transforming growth factor-β1 (TGF-β1) is an important step in the process of lung fibrosis, in which FGF-2, released by TGF-β1, is involved. sFGFR2c inhibited α-SMA induction by TGF-β1 via both the extracellular signal-regulated kinase 1/2 (ERK1/2) and Smad3 pathways in primary mouse lung fibroblasts and the proliferation of mouse lung fibroblasts. In a mouse model of bleomycin (BLM)-induced lung fibrosis, mice were treated with sFGFR2c from d 3 or d 10 to 31 after BLM administration. Then we used hematoxylin and eosin staining, Masson staining and immunohistochemical staining to evaluate the inhibitory effects of sFGFR2c on lung fibrosis. The treatment with sFGFR2c resulted in significant attenuation of the lung fibrosis score and collagen deposition. The expression levels of α-SMA, p-FGFRs, p-ERK1/2 and p-Smad3 in the lungs of sFGFR2c-treated mice were markedly lower. sFGFR2c may have potential for the treatment of lung fibrosis as an FGF-2 antagonist.

Notes

Acknowledgments

This work was funded by the Ministry of Science and Technology of China (2009ZX09103-632) and by the National Natural Science Foundation of China (91029742). We thank S Fenyong, W Xing and C Xiao-jia for technical help, invaluable discussions and reagents.

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Authors and Affiliations

  • Wang Ju
    • 1
  • Yu Zhihong
    • 1
  • Zhou Zhiyou
    • 1
  • Huang Qin
    • 1
  • Wang Dingding
    • 2
  • Sun Li
    • 1
  • Zhu Baowei
    • 1
  • Wei Xing
    • 1
  • He Ying
    • 1
  • Hong An
    • 1
  1. 1.Guangdong Provincial Key Laboratory of Bioengineering Medicine (National Engineering Research Centre of Genetic Medicine)Guangzhou, GuangdongChina
  2. 2.Department of Biotechnology, Institute of Life Science and Biological Pharmacy, Guangdong Pharmaceutical UniversityGuangzhou Higher Education Mega CenterGuangzhou, GuangdongChina

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