Lipid Mediators Regulate Pulmonary Fibrosis: Potential Mechanisms and Signaling Pathways

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.

The Roles of Various Prostaglandins in Fibrosis: A Review

“…However, no effective treatments are available to prevent or reverse this process. Nintedanib and pirfenidone are the only two drugs approved by the Food and Drug Administration to treat IPF [ 3 ] but only retard disease progression. Therefore, a better understanding of the processes and mechanisms of fibrosis will help identify more specific and efficient strategies to reduce the morbidity and mortality caused by fibrosis.…”

Facts about Fats: New Insights into the Role of Lipids in Metabolism, Disease and Therapy

“…Among signaling molecules, eicosanoids seem to play crucial roles in the disease pathology, and a variety of reports suggest them as useful molecular targets for innovative therapeutic interventions. The involvement of lipid molecules as signaling mediators is further examined in the comprehensive review by Suryadevara et al, which collects up-to-date knowledge about the pathways mediated by lipid mediators in pulmonary fibrosis [19]. Indeed, the metabolism of phospholipids, sphingolipids, and polyunsaturated fatty acids may generate key molecules capable of signaling properties, which exhibit pro-and anti-fibrotic effects in patients and preclinical models of idiopathic pulmonary fibrosis (IPF).…”

A Ferroptosis-Related Gene Signature for Lung Function and Quality of Life in Patients with Idiopathic Pulmonary Fibrosis

“…ACSL1 plays a key role in fatty acid metabolism. Studies have found that lipid metabolism dysregulation play an important role in the pathogenesis of IPF [44,45]. In addition, the levels of stearic acid (the one of fatty acid) is down-regulated in IPF lung tissues than in control lung tissues, and further study found that stearic acid had anti brotic activity [45].…”