title: Lysophosphatidic acid-1-receptor targeting agents for fibrosis.
abstract: BACKGROUND
  The presence of fibrosis is associated with alterations in organ architecture and is responsible for the morbidity of diseases including pneumopathies, systemic sclerosis, liver cirrhosis, chronic cardiovascular diseases, progressive kidney diseases and diabetes. Although a growing number of pro-fibrotic molecules, mediators and other pathways have been reported, there are currently very few antifibrotic molecules being evaluated in clinical trials.
  
  
  METHODS
  Current knowledge about the contribution of lysophosphatidic acid (LPA), a bioactive mediator acting via specific G-protein coupled receptors (LPAR), in the etiology of fibrosis. In a number of organs, fibrosis is associated with increased LPA production as well as with increased expression of some LPAR subtypes (mainly LPA1R). LPAR(-/-) knockout mice and treatment of animal models with specific antagonists clearly demonstrate the contribution of LPA1R subtype to the development of kidney, lung, vascular and dermal fibrosis. The involvement of LPA in liver fibrosis is also strongly suspected but still unproven.
  
  
  CONCLUSIONS
  Experiments in animal models clearly demonstrate that LPA1R antagonists have interesting anti-fibrotic potencies. This reveals promising perspectives for the design of new therapeutic approaches to prevent fibrosis-associated diseases. Nevertheless, the number of efficient LPA1R antagonists currently available is still low, and none of them has been used in clinical trials so far.
authors: Inserm, Toulouse, France.
authors: Chloé
authors: C
authors: Rancoule
authors: Jean-Philippe
authors: JP
authors: Pradère
authors: Julien
authors: J
authors: Gonzalez
authors: Julie
authors: J
authors: Klein
authors: Philippe
authors: P
authors: Valet
authors: Jean-Loup
authors: JL
authors: Bascands
authors: Joost P
authors: JP
authors: Schanstra
authors: Jean-Sébastien
authors: JS
authors: Saulnier-Blache
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D005355:Fibrosis / Q000188:drug therapy*; D006801:Humans; D008246:Lysophospholipids / Q000037:antagonists & inhibitors / Q000378:metabolism; D058990:Molecular Targeted Therapy / Q000379:methods*; D049368:Receptors, Lysophosphatidic Acid / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D008246:Lysophospholipids; D049368:Receptors, Lysophosphatidic Acid; C032881:lysophosphatidic acid