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.
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.
| Original language | English |
|---|---|
| Pages (from-to) | 228-238 |
| Number of pages | 10 |
| Journal | Biochimica et Biophysica Acta Molecular and Cell Biology of Lipids |
| Volume | 1831 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2013 |
Keywords
- sphingosine 1-phosphate
- lysophosphatidic acid
- fibrosis
- connective tissue growth factor
- signalling