Pyne Nigel J, Dubois Gerald, Pyne Susan
University of Strathclyde, Glasgow, G4 0RE, UK.
Biochim Biophys Acta. 2013 Jan;1831(1):228-38. doi: 10.1016/j.bbalip.2012.07.003. Epub 2012 Jul 16.
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.
本综述强调了1-磷酸鞘氨醇（S1P）和溶血磷脂酸（LPA）在多种不同类型纤维化中所起的新作用。事实上，LPA和S1P均参与纤维化的多过程发病机制，涉及促进已明确的成纤维细胞向肌成纤维细胞分化过程以及更具争议性的上皮-间质转化和纤维细胞归巢至纤维化病灶的过程。因此，针对这些生物活性溶血脂质的产生或阻断其作用位点/机制具有治疗潜力。确实，LPA受体1（LPA(1)）选择性拮抗剂目前正在研发用于治疗肺纤维化，以及一种正在进行1期临床试验用于治疗年龄相关性黄斑变性的抗S1P中和抗体。因此，针对LPA和S1P的治疗方法可能距离临床应用不远了。本文是名为《溶血磷脂研究进展》的特刊的一部分。
