Lipid mediators regulate pulmonary fibrosis: Potential mechanisms and signaling pathways

Vidyani Suryadevara, Ramaswamy Ramchandran, David W. Kamp, Viswanathan Natarajan*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

7 Scopus citations

Abstract

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease of unknown etiology characterized by distorted distal lung architecture, inflammation, and fibrosis. The molecular mechanisms involved in the pathophysiology of IPF are incompletely defined. Several lung cell types including alveolar epithelial cells, fibroblasts, monocyte-derived macrophages, and endothelial cells have been implicated in the development and progression of fibrosis. Regardless of the cell types involved, changes in gene expression, disrupted glycolysis, and mitochondrial oxidation, dysregulated protein folding, and altered phospholipid and sphingolipid metabolism result in activation of myofibroblast, deposition of extracellular matrix proteins, remodeling of lung architecture and fibrosis. Lipid mediators derived from phospholipids, sphingolipids, and polyunsaturated fatty acids play an important role in the pathogenesis of pulmonary fibrosis and have been described to exhibit pro-and anti-fibrotic effects in IPF and in preclinical animal models of lung fibrosis. This review describes the current understanding of the role and signaling pathways of prostanoids, lysophospholipids, and sphingolipids and their metabolizing enzymes in the development of lung fibrosis. Further, several of the lipid mediators and enzymes involved in their metabolism are therapeutic targets for drug development to treat IPF.

Original languageEnglish (US)
Article number4257
Pages (from-to)1-46
Number of pages46
JournalInternational journal of molecular sciences
Volume21
Issue number12
DOIs
StatePublished - Jun 2 2020

Keywords

  • Autotaxin
  • G-protein coupled receptors
  • Lipid mediators
  • Lysocardiolipin acyltransferase
  • Lysophosphatidic acid
  • Oxidized phospholipids
  • Phospholipase D
  • Prostaglandins
  • Pulmonary fibrosis
  • Sphingolipids
  • Sphingosine kinase 1
  • Sphingosine-1-phosphate

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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