Inhibition of Wnt/β-catenin signaling suppresses bleomycin-induced pulmonary fibrosis by attenuating the expression of TGF-β1 and FGF-2

Xiang Chen, Chaowen Shi, Xiannan Meng, Kaijia Zhang, Xiaoyao Li, Cong Wang, Zou Xiang, Kebin Hu, Xiaodong Han

Research output: Journal article publicationJournal articleAcademic researchpeer-review

41 Citations (Scopus)

Abstract

Pulmonary fibrosis is a progressive lung disorder of unknown etiology, which is characterized by alterations in alveolar epithelium function, fibroblast activation, and increased extracellular matrix deposition. Recent studies have demonstrated that PF is associated with uncontrolled production of cytokines after lung injury. In the present study, we found that transforming growth factor-β1 (TGF-β1) and fibroblast growth factor 2 (FGF-2) were both upregulated in bleomycin-induced fibrotic lung tissue and primary murine alveolar epithelial Type II (ATII) cells treated with bleomycin. Furthermore, we discovered that TGF-β1 could induce the differentiation of lung resident mesenchymal stem cells (LR-MSCs) into fibroblasts, which may play an essential role in PF. LR-MSCs incubated with FGF-2 showed modest alterations in the expression of α-SMA and Vimentin. Moreover, in our study, we found that Wnt/β-catenin signaling was activated both in vitro and in vivo as a result of bleomycin treatment. Interestingly, we also found that suppression of the Wnt/β-catenin signaling could significantly attenuate bleomycin-induced PF accompanied with decreased expression of TGF-β1 and FGF-2 in vitro and in vivo. These results support that controlling the aberrant expression of TGF-β1 and FGF-2 via inhibition of Wnt/β-catenin signaling could serve as a potential therapeutic strategy for PF.

Original languageEnglish
Pages (from-to)22-30
Number of pages9
JournalExperimental and Molecular Pathology
Volume101
Issue number1
Early online date23 Apr 2016
DOIs
Publication statusPublished - 1 Aug 2016
Externally publishedYes

Keywords

  • Alveolar epithelial type II cells (ATII cells)
  • Fibroblast growth factor (FGF)-2
  • Fibroblastic differentiation
  • Lung resident mesenchymal stem cells (LR-MSCs)
  • Transforming growth factor (TGF)-β1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Clinical Biochemistry

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