Role of sphingosine 1-phosphate and lysophosphatidic acid in fibrosis.

Nigel J Pyne, Gerald Dubois, Susan Pyne

University of Strathclyde, Glasgow, G4 0RE, UK. n.j.pyne@strath.ac.uk

Biochimica et biophysica acta 2013 Jan

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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. Copyright © 2012 Elsevier B.V. All rights reserved.

Citation

Nigel J Pyne, Gerald Dubois, Susan Pyne. Role of sphingosine 1-phosphate and lysophosphatidic acid in fibrosis. Biochimica et biophysica acta. 2013 Jan;1831(1):228-38