Role of sphingosine 1-phosphate and lysophosphatidic acid in fibrosis.
This review highlights an emerging role for sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) in many different types of fibrosis. Indeed, both LPA and S1P are involved in the multi-process pathogenesis of fibrosis, being implicated in promoting the well-established process of differentiation of fibroblasts to myofibroblasts and the more controversial epithelial-mesenchymal transition and homing of fibrocytes to fibrotic lesions. Therefore, targeting the production of these bioactive lysolipids or blocking their sites/mechanisms of action has therapeutic potential. Indeed, LPA receptor 1 (LPA(1)) selective antagonists are currently being developed for the treatment of fibrosis of the lung as well as a neutralising anti-S1P antibody that is currently in Phase 1 clinical trials for treatment of age related macular degeneration. Thus, LPA- and S1P-directed therapeutics may not be too far from the clinic. This article is part of a Special Issue entitled Advances in Lysophospholipid Research.
University of Strathclyde, Glasgow, G4 0RE, UK. n.j.pyne@strath.ac.uk
Nigel J
NJ
Pyne
Gerald
G
Dubois
Susan
S
Pyne
D000818:Animals; D005355:Fibrosis / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism*; D008954:Models, Biological; D009928:Organ Specificity; D049349:Receptors, Lysosphingolipid / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism
D008246:Lysophospholipids; D049349:Receptors, Lysosphingolipid; C060506:sphingosine 1-phosphate; D013110:Sphingosine; C032881:lysophosphatidic acid