Evaluation of prevention and treatment effects of fibroblast growth factor-21 in BLM-induced pulmonary fibrosis

Naunyn Schmiedebergs Arch Pharmacol. 2023 Nov;396(11):3299-3313. doi: 10.1007/s00210-023-02540-3. Epub 2023 May 31.

Abstract

Pulmonary fibrosis is a progressive and fatal fibrotic lung disease and associated with a high mortality rate. In the study, the prevention and treatment effects of fibroblast growth factor-21 (FGF-21) in bleomycin (BLM)-induced pulmonary fibrosis were investigated in vivo and vitro. In the prevention of pulmonary fibrosis studies, the results showed that interdict of FGF-21 could reduce the related gene and protein expression levels of pulmonary fibrosis. In addition, FGF-21 significantly reduced both the aggregation of inflammatory cells and deposition of collagen in the lung by histopathology. In therapy of pulmonary fibrosis studies, the results indicated that treatment with FGF-21 resulted in an amelioration of the pulmonary fibrosis in mice with reductions of the pathological score, collagen deposition and transforming growth factor (TGF)-β and α-smooth muscle actin (α-SMA) expressions in the lung tissues at fibrotic stage, and late administration was also able to reduce the degree of pulmonary fibrosis and even better than these in the prevention group. Furthermore, BLM-induced THP-1 macrophage model was verified using FGF-21; the result showed that FGF-21 decreased the related gene expression level of pulmonary fibrosis. FGF-21 may have preventive and therapeutic effects on BLM-induced pulmonary fibrosis via inhibiting myofibroblast differentiation and inflammatory. Thus, FGF-21 represents a potential drug for the prevention and treatment of pulmonary fibrosis.

Keywords: Fibroblast growth factor-21; Inflammatory response; Pulmonary fibrosis; TGF-β; α-SMA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bleomycin / adverse effects
  • Collagen / metabolism
  • Fibroblast Growth Factors / pharmacology
  • Fibroblasts
  • Fibrosis
  • Lung
  • Mice
  • Mice, Inbred C57BL
  • Pulmonary Fibrosis* / chemically induced
  • Pulmonary Fibrosis* / drug therapy
  • Pulmonary Fibrosis* / prevention & control
  • Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta1 / metabolism

Substances

  • Bleomycin
  • fibroblast growth factor 21
  • Fibroblast Growth Factors
  • Transforming Growth Factor beta
  • Collagen
  • Transforming Growth Factor beta1