The Role of Sphingolipids in Regulating Vascular Permeability in Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a disease that causes scarring and fibrotic transformation of the lung parenchyma, resulting in the progressive loss of respiratory function and, often, death. Current treatments that target profibrotic factors can slow the rate of progression but are unable to ultimately stop it. In the past decade, many studies have shown that increased vascular permeability may be both a predictive and perpetuating factor in fibrogenesis. Consequently, there is a search for therapeutic targets to try and modulate vascular permeability in fibrotic lungs. One such class of targets that show great promise is sphingolipids. Sphingolipids are common in cell membranes and are increasingly recognized as critical to many cell signaling pathways, including those that affect the integrity of the vascular endothelial barrier. In this focused review we look at sphingolipids, particularly the sphingosine-1-phosphate (S1P) axis and its effects on vascular permeability, and how those effects may affect the pathogenesis of IPF. We further examine existing S1P modulators and their potential efficacy as therapeutics for IPF.

Automated summary

Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by scarring and fibrotic transformation of the lung, leading to respiratory function loss and often death. Increased vascular permeability has been identified as a contributing factor to fibrogenesis. Sphingolipids, particularly the sphingosine-1-phosphate (S1P) axis, play a critical role in cell signaling pathways affecting vascular endothelial integrity. This review focuses on the role of sphingolipids in IPF pathogenesis and explores the potential of S1P modulators as therapeutic targets for IPF.