Pulmonary autotaxin expression contributes to the pathogenesis of pulmonary fibrosis

Am J Respir Cell Mol Biol. 2012 Nov;47(5):566-74. doi: 10.1165/rcmb.2012-0004OC. Epub 2012 Jun 28.


Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic form of diffuse lung disease occurring mainly in older adults. Increased lysophosphatidic acid (LPA) concentrations have been reported in the alveolar space of both idiopathic pulmonary fibrosis patients and a corresponding animal model, whereas the genetic deletion or pharmacological inhibition of LPA receptor 1 attenuated the development of the modeled disease, suggesting a direct involvement of LPA in disease pathogenesis. In this report, increased concentrations of autotaxin (ATX; ENPP2), the enzyme largely responsible for extracellular LPA production, were detected in both murine and human fibrotic lungs. The genetic deletion of ATX from bronchial epithelial cells or macrophages attenuated disease severity, establishing ATX as a novel player in IPF pathogenesis. Furthermore, the pharmacological inhibition of ATX attenuated the development of the modeled disease, suggesting that ATX is a possible therapeutic target in IPF.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anilides / pharmacology
  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Female
  • Gene Expression
  • Gene Knockout Techniques
  • Humans
  • Idiopathic Pulmonary Fibrosis / enzymology*
  • Idiopathic Pulmonary Fibrosis / pathology
  • Lung / enzymology*
  • Lysophospholipids / metabolism
  • Macrophages, Alveolar / enzymology
  • Macrophages, Alveolar / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Middle Aged
  • Organophosphonates / pharmacology
  • Phosphodiesterase Inhibitors / pharmacology
  • Phosphoric Diester Hydrolases / genetics
  • Phosphoric Diester Hydrolases / metabolism*
  • Respiratory Mucosa / enzymology
  • Respiratory Mucosa / pathology


  • Anilides
  • Lysophospholipids
  • Organophosphonates
  • Phosphodiesterase Inhibitors
  • Phosphoric Diester Hydrolases
  • alkylglycerophosphoethanolamine phosphodiesterase
  • lysophosphatidic acid