[Regulation of airway stem cell proliferation in idiopathic pulmonary fibrosis]

Zhonghua Jie He He Hu Xi Za Zhi. 2016 Sep;39(9):714-8. doi: 10.3760/cma.j.issn.1001-0939.2016.09.011.
[Article in Chinese]

Abstract

Objective: To investigate the effect of fibroblasts on regulating airway stem cell proliferation in idiopathic pulmonary fibrosis.

Methods: Lung cell suspension was prepared from β-actin-GFP mice. Airway stem cells were obtained by fluorescence activated cell sorting and co-cultured with lung fibroblasts. The fibroblasts were treated with TGF-β inhibitor SB43142. The expression of growth factors FGF1/2 and the effect of FGF1/2 on stem cell proliferation were observed.

Results: The cloning efficiency of airway stem cells, when co-cultured with normal lung fibroblast cells for 8 days, was (3.5±1.1)%, while the cloning efficiency was reduced to (0.04±0.04)% when co-cultured with lung fibroblasts from idiopathic pulmonary fibrosis patients. The difference between the 2 groups was statistically significant(P=0.002 5). TGF-β receptor inhibitor SB431542 increased lung fibroblast growth factors FGF1/2 expression.FGF1 mRNA expression was increased to the experimental group 0.005 5 from 0.000 2 in the control group.FGF2 mRNA expression of the amount raised to the experimental group 0.000 15 from 0.000 8 in the control group.FGF1/2 promoted the growth of airway stem cells. After FGF1/2 was co-cultured with normal lung fibroblast cells for 8 days, the cloning efficiency of airway stem cells was (0.3±0.1)%.

Conclusion: During the development of idiopathic pulmonary fibrosis, fibroblast secreted FGF1/2 regulate airway stem cell proliferation.

MeSH terms

  • Actins / genetics
  • Actins / metabolism
  • Animals
  • Benzamides
  • Cell Movement / physiology
  • Cell Proliferation / drug effects*
  • Cells, Cultured / drug effects
  • Dioxoles
  • Fibroblast Growth Factor 1 / biosynthesis
  • Fibroblast Growth Factor 1 / pharmacology*
  • Fibroblast Growth Factor 2 / biosynthesis
  • Fibroblast Growth Factor 2 / pharmacology*
  • Fibroblasts
  • Gene Expression Regulation / drug effects
  • Humans
  • Idiopathic Pulmonary Fibrosis / genetics
  • Idiopathic Pulmonary Fibrosis / metabolism*
  • Idiopathic Pulmonary Fibrosis / pathology
  • Lung / metabolism
  • Lung / pathology
  • Mice
  • MicroRNAs / genetics*
  • Protein Serine-Threonine Kinases
  • Pulmonary Fibrosis
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Fibroblast Growth Factor / biosynthesis*
  • Receptors, Fibroblast Growth Factor / drug effects
  • Receptors, Fibroblast Growth Factor / genetics
  • Receptors, Fibroblast Growth Factor / physiology
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta

Substances

  • 4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide
  • Actins
  • Benzamides
  • Dioxoles
  • MicroRNAs
  • Receptors, Fibroblast Growth Factor
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • Fibroblast Growth Factor 2
  • Fibroblast Growth Factor 1
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II