Lipids and eicosanoids in fibrosis:  emerging targets for therapy.
OBJECTIVE
Lipid mediators including the lysophospholipids, sphingolipids and eicosanoids have long been implicated in inflammation, cancer and numerous other diseases. Over the last decade, new research suggests a role for these mediators in fibrosis.


RESULTS
Recent developments in the study of fibrotic mediators have centered on lysophospholipids and eicosanoids. New research is evaluating metabolic-profiling strategies to quantitatively measure lipid mediators in human plasma. Lysophosphatidic acid receptor antagonists are currently under development with early phase trials scheduled for idiopathic pulmonary fibrosis and scleroderma dermal fibrosis. Eicosanoids have long been implicated in maintaining tissue homeostasis, and the balance of profibrotic and antifibrotic effects has drawn attention in recent years. Targeting the prostanoids, specifically PGE2 and PGI2, as well as the leukotrienes is now being considered for antifibrotic therapies.


CONCLUSIONS
Lipid mediators have significant roles in many disease processes. Significant research now suggests a critical role for these mediators in the pathogenesis of fibrosis. Targeting these mediators is a promising area of drug discovery.
Division of Rheumatology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA. fcastelino@partners.org
Flavia V
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Castelino
D000818:Animals; D004195:Disease Models, Animal; D015777:Eicosanoids / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000188:drug therapy / Q000378:metabolism; D018836:Inflammation Mediators / Q000627:therapeutic use*; D008246:Lysophospholipids / Q000378:metabolism*; D011658:Pulmonary Fibrosis / Q000378:metabolism*; D049368:Receptors, Lysophosphatidic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000150:complications / Q000188:drug therapy / Q000378:metabolism
D015777:Eicosanoids; D018836:Inflammation Mediators; D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid