Role of sphingosine 1-phosphate and lysophosphatidic acid in fibrosis

Nigel Pyne, Gerald Dubois, Susan Pyne

Research output: Contribution to journalSpecial issue

31 Citations (Scopus)

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.
LanguageEnglish
Pages228-238
Number of pages10
JournalBiochimica et Biophysica Acta Molecular and Cell Biology of Lipids
Volume1831
Issue number1
DOIs
Publication statusPublished - Jan 2013

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Fibrosis
Lysophosphatidic Acid Receptors
Myofibroblasts
Macular Degeneration
Antibodies
Therapeutics
lysophosphatidic acid
sphingosine 1-phosphate

Keywords

  • sphingosine 1-phosphate
  • lysophosphatidic acid
  • fibrosis
  • connective tissue growth factor
  • signalling

Cite this

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title = "Role of sphingosine 1-phosphate and lysophosphatidic acid in fibrosis",
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 offibroblasts to myofibroblasts and the more controversial epithelial-mesenchymaltransition and homing of fibrocytes to fibrotic lesions. Therefore, targeting theproduction of these bioactive lysolipids or blocking their sites/mechanisms ofaction has therapeutic potential. Indeed, LPA receptor 1 (LPA(1)) selectiveantagonists are currently being developed for the treatment of fibrosis of thelung as well as a neutralising anti-S1P antibody that is currently in Phase 1clinical trials for treatment of age related macular degeneration. Thus, LPA- andS1P-directed therapeutics may not be too far from the clinic.",
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Role of sphingosine 1-phosphate and lysophosphatidic acid in fibrosis. / Pyne, Nigel; Dubois, Gerald; Pyne, Susan.

In: Biochimica et Biophysica Acta Molecular and Cell Biology of Lipids, Vol. 1831, No. 1, 01.2013, p. 228-238.

Research output: Contribution to journalSpecial issue

TY - JOUR

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AU - Dubois, Gerald

AU - Pyne, Susan

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AB - 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 offibroblasts to myofibroblasts and the more controversial epithelial-mesenchymaltransition and homing of fibrocytes to fibrotic lesions. Therefore, targeting theproduction of these bioactive lysolipids or blocking their sites/mechanisms ofaction has therapeutic potential. Indeed, LPA receptor 1 (LPA(1)) selectiveantagonists are currently being developed for the treatment of fibrosis of thelung as well as a neutralising anti-S1P antibody that is currently in Phase 1clinical trials for treatment of age related macular degeneration. Thus, LPA- andS1P-directed therapeutics may not be too far from the clinic.

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