Chrysophanol administration alleviates bleomycin-induced pulmonary fibrosis by inhibiting lung fibroblast proliferation and Wnt/β-catenin signaling

  • Xiangwei Qi
  • Yamei Ou
  • Ying Xie
  • Kangrong Cai
  • Hualin Gan
  • Qiqi Wan
  • Hao Xie
  • Zeqing Song
Keywords: Chrysophanol, Bleomycin, Pulmonary fibrosis, Hydroxyproline, E-cadherin

Abstract

Purpose: To determine the functional effect of chrysophanol (CH) on bleomycin (BLM)-induced pulmonary fibrosis (PF) and reveal its mechanism of action.
Methods: A mouse model of PF was established by intratracheal instillation of BLM (5 mg/kg), prior to CH administration. Masson’s trichrome staining was used to analyze interstitial fibrosis and collagen deposition. Hydroxyproline (HYP) content was measured, and lung fibroblast viability determined by MTT assay. Bronchoalveolar lavage fluid (BALF) was collected, and levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and interferon-γ (IFN-γ) were evaluated using enzyme-linked immunosorbent assays (ELISA). Expression of cell signaling, adhesion, and apoptotic proteins were determined by western blotting.
Results: Administration of CH reduced collagen deposition and HYP content, downregulated α-smooth muscle actin, upregulated E-cadherin, and decreased the levels of TNF-α, IL-1β, IL-6, and IFN-γ in BLM-treated mice. The viability of lung fibroblasts was also reduced, and Bcl-2-associated X protein and cleaved caspase-3 were upregulated after CH treatment in BLM-treated mice. In addition, CH treatment in BLM-treated mice significantly increased levels of cytoplasmic β-catenin but decreased its expression in the nucleus.
Conclusion: Administration of CH alleviated BLM-induced PF by inhibiting lung fibroblast proliferation and nuclear translocation of β-catenin. Thus, this study provides a potential therapeutic strategy for PF.

Keywords: Chrysophanol, Bleomycin, Pulmonary fibrosis, Hydroxyproline, E-cadherin

Published
2020-06-26
Section
Articles

Journal Identifiers


eISSN: 1596-9827
print ISSN: 1596-5996