Lysophospholipid Mediators in Health and Disease

Lysophospholipids, exemplified by lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), are produced by the metabolism and perturbation of biological membranes. Both molecules are established extracellular lipid mediators that signal via specific G protein-coupled receptors in vertebrates. This widespread signaling axis regulates the development, physiological functions, and pathological processes of all organ systems. Indeed, recent research into LPA and S1P has revealed their important roles in cellular stress signaling, inflammation, resolution, and host defense responses. In this review, we focus on how LPA regulates fibrosis, neuropathic pain, abnormal angiogenesis, endometriosis, and disorders of neuroectodermal development such as hydrocephalus and alopecia. In addition, we discuss how S1P controls collective behavior, apoptotic cell clearance, and immunosurveillance of cancers. Advances in lysophospholipid research have led to new therapeutics in autoimmune diseases, with many more in earlier stages of development for a wide variety of diseases, such as fibrotic disorders, vascular diseases, and cancer.

Automated summary

Lysophospholipids, such as lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), are important extracellular lipid mediators that signal through specific G protein-coupled receptors. They play crucial roles in various biological processes and diseases, including cellular stress signaling, inflammation, and host defense responses. LPA is involved in regulating fibrosis, neuropathic pain, abnormal angiogenesis, endometriosis, and neuroectodermal developmental disorders, while S1P controls collective behavior, apoptotic cell clearance, and immunesurveillance of cancers. The study of lysophospholipids has led to the development of new therapeutics for autoimmune diseases and holds promise for future treatments of fibrotic disorders, vascular diseases, and cancer.