Fibroblast growth factors and pulmonary fibrosis: it's more complex than it sounds

J Pathol. 2017 Jan;241(1):6-9. doi: 10.1002/path.4825. Epub 2016 Nov 29.

Abstract

Lung fibrosis results from the cumulative effect of dysfunctional wound repair involving multiple cell types, including fibroblasts, epithelial cells, and macrophages responding to an array of soluble and matrix-mediated stimuli. Recent studies have shown that a tyrosine kinase inhibitor that targets FGF, VEGF, and PDGF receptors can slow the rate of decline in pulmonary function in patients with idiopathic pulmonary fibrosis. However, each of these growth factor families is comprised of multiple ligands and receptors with pleiotropic activities on different cell types such that their broad inhibition might have both pro-fibrotic and anti-fibrotic effects, limiting the potential therapeutic efficacy. Continued investigation and delineation of specific roles of individual proteins and receptors on different cell types hold promise for targeting specific pathways with precision and optimizing the potential efficacy of future approaches to lung fibrosis therapy. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Keywords: EMT; fibroblast growth factor; fibrosis; idiopathic pulmonary fibrosis; nintedanib; precision medicine.

MeSH terms

  • Enzyme Inhibitors / therapeutic use
  • Fibroblast Growth Factors / physiology*
  • Humans
  • Idiopathic Pulmonary Fibrosis / drug therapy
  • Idiopathic Pulmonary Fibrosis / metabolism*
  • Idiopathic Pulmonary Fibrosis / pathology
  • Indoles / therapeutic use
  • Molecular Targeted Therapy / methods
  • Receptors, Fibroblast Growth Factor / antagonists & inhibitors

Substances

  • Enzyme Inhibitors
  • Indoles
  • Receptors, Fibroblast Growth Factor
  • Fibroblast Growth Factors
  • nintedanib