Idiopathic pulmonary fibrosis: Epithelial-mesenchymal interactions and emerging therapeutic targets

Matrix Biol. 2018 Oct:71-72:112-127. doi: 10.1016/j.matbio.2018.03.021. Epub 2018 Apr 3.

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic fibrotic disease of the lung that is marked by progressive decline in pulmonary function and ultimately respiratory failure. Genetic and environmental risk factors have been identified that indicate injury to, and dysfunction of the lung epithelium is central to initiating the pathogenic process. Following injury to the lung epithelium, growth factors, matrikines and extracellular matrix driven signaling together activate a variety of repair pathways that lead to inflammatory cell recruitment, fibroblast proliferation and expansion of the extracellular matrix, culminating in tissue fibrosis. This tissue fibrosis then leads to changes in the biochemical and biomechanical properties of the extracellular matrix, which potentiate profibrotic mechanisms through a "feed-forward cycle." This review provides an overview of the interactions of the pathogenic mechanisms of IPF with a focus on epithelial-mesenchymal crosstalk and the extracellular matrix as a therapeutic target for idiopathic pulmonary fibrosis.

Keywords: Genetics; IPF; Interstitial lung disease; Matrix; Treatment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Epithelial-Mesenchymal Transition* / drug effects
  • Extracellular Matrix / metabolism*
  • Humans
  • Idiopathic Pulmonary Fibrosis / drug therapy
  • Idiopathic Pulmonary Fibrosis / etiology*
  • Idiopathic Pulmonary Fibrosis / metabolism
  • Idiopathic Pulmonary Fibrosis / physiopathology
  • Lung / metabolism
  • Lung / physiopathology
  • Molecular Targeted Therapy
  • Signal Transduction