Prostaglandin E2 and the pathogenesis of pulmonary fibrosis

Am J Respir Cell Mol Biol. 2011 Sep;45(3):445-52. doi: 10.1165/rcmb.2011-0025RT. Epub 2011 Mar 18.

Abstract

Prostaglandin (PG)E(2) is a bioactive eicosanoid that regulates many biologically important processes in part due to its ability to signal through four distinct G-protein-coupled receptors with differential signaling activity and unique expression patterns in different cell types. Although PGE(2) has been linked to malignancy in many organs, it is believed to play a beneficial role in the setting of fibrotic lung disease. This is in part due to the ability of PGE(2) to limit many of the pathobiologic features of lung fibroblasts and myofibroblasts, including the ability of PGE(2) to limit fibroblast proliferation, migration, collagen secretion, and, as originally reported in the Journal by us in 2003, the ability to limit transforming growth factor (TGF)-β-induced myofibroblast differentiation. In the setting of lung fibrosis, PGE(2) production and signaling is often diminished. In the last 8 years, significant advances have been made to better understand the dysregulation of PGE(2) production and signaling in the setting of lung fibrosis. We also have a clearer picture of how PGE(2) inhibits myofibroblast differentiation and the receptor signaling pathways that can influence fibroblast proliferation. This review highlights these recent advances and offers new insights into the potential ways that PGE(2) and its downstream signals can be regulated for therapeutic benefit in a disease that has no validated treatment options.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cell Adhesion
  • Cell Differentiation
  • Cell Movement
  • Cell Proliferation
  • Dinoprostone / metabolism*
  • Epigenesis, Genetic
  • Fibroblasts / cytology
  • Gene Expression Regulation*
  • Humans
  • Models, Biological
  • Protein Structure, Tertiary
  • Pulmonary Fibrosis / pathology*
  • Signal Transduction
  • Transforming Growth Factor beta / metabolism

Substances

  • Transforming Growth Factor beta
  • Dinoprostone