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Lipid Mediators Regulate Pulmonary Fibrosis: Potential Mechanisms and Signaling Pathways
- Source :
- International Journal of Molecular Sciences, Vol 21, Iss 4257, p 4257 (2020), International Journal of Molecular Sciences
- Publication Year :
- 2020
- Publisher :
- MDPI AG, 2020.
-
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.
- Subjects :
- autotaxin
sphingosine kinase 1
Review
lipid mediators
prostaglandins
lcsh:Chemistry
Idiopathic pulmonary fibrosis
chemistry.chemical_compound
Fibrosis
Pulmonary fibrosis
Medicine
phospholipase D
Gene Regulatory Networks
lcsh:QH301-705.5
Spectroscopy
General Medicine
respiratory system
Computer Science Applications
medicine.anatomical_structure
G-protein coupled receptors
oxidized phospholipids
lipids (amino acids, peptides, and proteins)
Myofibroblast
Glycolysis
Signal Transduction
Catalysis
Inorganic Chemistry
Animals
Humans
Sphingosine-1-phosphate
Physical and Theoretical Chemistry
Molecular Biology
Lung
sphingolipids
pulmonary fibrosis
business.industry
Organic Chemistry
Lipid signaling
medicine.disease
Lipid Metabolism
Sphingolipid
Idiopathic Pulmonary Fibrosis
respiratory tract diseases
Disease Models, Animal
chemistry
Gene Expression Regulation
lcsh:Biology (General)
lcsh:QD1-999
Cancer research
sphingosine-1-phosphate
lysocardiolipin acyltransferase
business
lysophosphatidic acid
Subjects
Details
- Language :
- English
- ISSN :
- 16616596 and 14220067
- Volume :
- 21
- Issue :
- 4257
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....b5b9b93c94d07e99dadb870d42371dca