TGF beta inhibits HGF, FGF7, and FGF10 expression in normal and IPF lung fibroblasts

Physiol Rep. 2018 Aug;6(16):e13794. doi: 10.14814/phy2.13794.

Abstract

TGF beta is a multifunctional cytokine that is important in the pathogenesis of pulmonary fibrosis. The ability of TGF beta to stimulate smooth muscle actin and extracellular matrix gene expression in fibroblasts is well established. In this report, we evaluated the effect of TGF beta on the expression of HGF, FGF7 (KGF), and FGF10, important growth and survival factors for the alveolar epithelium. These growth factors are important for maintaining type II cells and for restoration of the epithelium after lung injury. Under conditions of normal serum supplementation or serum withdrawal TGF beta inhibited fibroblast expression of HGF, FGF7, and FGF10. We confirmed these observations with genome wide RNA sequencing of the response of control and IPF fibroblasts to TGF beta. In general, gene expression in IPF fibroblasts was similar to control fibroblasts. Reduced expression of HGF, FGF7, and FGF10 is another means whereby TGF beta impairs epithelial healing and promotes fibrosis after lung injury.

Keywords: Idiopathic pulmonary fibrosis; KGF; pulmonary fibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cells, Cultured
  • Culture Media, Serum-Free
  • Female
  • Fibroblast Growth Factor 10 / biosynthesis
  • Fibroblast Growth Factor 10 / genetics
  • Fibroblast Growth Factor 7 / biosynthesis
  • Fibroblast Growth Factor 7 / genetics
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Gene Expression Regulation / drug effects
  • Hepatocyte Growth Factor / biosynthesis
  • Hepatocyte Growth Factor / genetics
  • Humans
  • Idiopathic Pulmonary Fibrosis / metabolism
  • Idiopathic Pulmonary Fibrosis / pathology*
  • Intercellular Signaling Peptides and Proteins / biosynthesis*
  • Intercellular Signaling Peptides and Proteins / genetics
  • Lung / metabolism
  • Male
  • Middle Aged
  • RNA, Messenger / genetics
  • Transforming Growth Factor beta / pharmacology*
  • Transforming Growth Factor beta / physiology

Substances

  • Culture Media, Serum-Free
  • FGF10 protein, human
  • FGF7 protein, human
  • Fibroblast Growth Factor 10
  • HGF protein, human
  • Intercellular Signaling Peptides and Proteins
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Fibroblast Growth Factor 7
  • Hepatocyte Growth Factor