Role of sphingosine 1-phosphate and lysophosphatidic acid in fibrosis

Pyne, Nigel and Dubois, Gerald and Pyne, Susan (2013) Role of sphingosine 1-phosphate and lysophosphatidic acid in fibrosis. Biochimica et Biophysica Acta Molecular and Cell Biology of Lipids, 1831 (1). pp. 228-238. ISSN 1388-1981 (https://doi.org/10.1016/j.bbalip.2012.07.003)

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Abstract

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.

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