1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Pathology: Mechanisms of Disease
  4. Volume 17, 2022
  5. Article

Annual Review of Pathology: Mechanisms of Disease

Volume 17, 2022

Lysophospholipid Mediators in Health and Disease

Abstract

Lysophospholipids, exemplified by lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P), are produced by the metabolism and perturbation of biological membranes. Both molecules are established extracellular lipid mediators that signal via specific G protein–coupled receptors in vertebrates. This widespread signaling axis regulates the development, physiological functions, and pathological processes of all organ systems. Indeed, recent research into LPA and S1P has revealed their important roles in cellular stress signaling, inflammation, resolution, and host defense responses. In this review, we focus on how LPA regulates fibrosis, neuropathic pain, abnormal angiogenesis, endometriosis, and disorders of neuroectodermal development such as hydrocephalus and alopecia. In addition, we discuss how S1P controls collective behavior, apoptotic cell clearance, and immunosurveillance of cancers. Advances in lysophospholipid research have led to new therapeutics in autoimmune diseases, with many more in earlier stages of development for a wide variety of diseases, such as fibrotic disorders, vascular diseases, and cancer.

Keyword(s): cancer, fibrosis, immunology, lysophosphatidic acid, lysophospholipids, sphingosine 1-phosphate, vascular biology
Loading

Article metrics loading...

/content/journals/10.1146/annurev-pathol-050420-025929
2022-01-24
2024-04-26
Loading full text...

Full text loading...

/deliver/fulltext/pathmechdis/17/1/annurev-pathol-050420-025929.html?itemId=/content/journals/10.1146/annurev-pathol-050420-025929&mimeType=html&fmt=ahah

Literature Cited

  1. 1. 
    Moolenaar WH, van Meeteren LA, Giepmans BN. 2004. The ins and outs of lysophosphatidic acid signaling. Bioessays 26:870–81
     [Google Scholar]
  2. 2. 
    Kihara Y, Maceyka M, Spiegel S, Chun J 2014. Lysophospholipid receptor nomenclature review: IUPHAR Review 8. Br. J. Pharmacol. 171:3575–94
     [Google Scholar]
  3. 3. 
    Aikawa S, Hashimoto T, Kano K, Aoki J 2015. Lysophosphatidic acid as a lipid mediator with multiple biological actions. J. Biochem. 157:81–89
     [Google Scholar]
  4. 4. 
    Cartier A, Hla T. 2019. Sphingosine 1-phosphate: lipid signaling in pathology and therapy. Science 366:eaar5551
     [Google Scholar]
  5. 5. 
    Engelbrecht E, MacRae CA, Hla T. 2021. Lysolipids in vascular development, biology, and disease. Arterioscler. Thromb. Vasc. Biol. 41:2564–84
     [Google Scholar]
  6. 6. 
    Proia RL, Hla T. 2015. Emerging biology of sphingosine-1-phosphate: its role in pathogenesis and therapy. J. Clin. Investig. 125:1379–87
     [Google Scholar]
  7. 7. 
    Chargaff E, Cohen SS. 1939. On lysophosphatides. J. Biol. Chem. 129:619–28
     [Google Scholar]
  8. 8. 
    Tokumura A, Fukuzawa K, Tsukatani H. 1978. Effects of synthetic and natural lysophosphatidic acids on the arterial blood pressure of different animal species. Lipids 13:572–74
     [Google Scholar]
  9. 9. 
    van Corven EJ, Groenink A, Jalink K, Eichholtz T, Moolenaar WH 1989. Lysophosphatidate-induced cell proliferation: identification and dissection of signaling pathways mediated by G proteins. Cell 59:45–54
     [Google Scholar]
  10. 10. 
    Hecht JH, Weiner JA, Post SR, Chun J. 1996. Ventricular zone gene-1 (vzg-1) encodes a lysophosphatidic acid receptor expressed in neurogenic regions of the developing cerebral cortex. J. Cell Biol. 135:1071–83
     [Google Scholar]
  11. 11. 
    Bandoh K, Aoki J, Hosono H, Kobayashi S, Kobayashi T et al. 1999. Molecular cloning and characterization of a novel human G-protein-coupled receptor, EDG7, for lysophosphatidic acid. J. Biol. Chem. 274:27776–85
     [Google Scholar]
  12. 12. 
    Hla T, Maciag T. 1990. An abundant transcript induced in differentiating human endothelial cells encodes a polypeptide with structural similarities to G-protein-coupled receptors. J. Biol. Chem. 265:9308–13
     [Google Scholar]
  13. 13. 
    Lee MJ, Van Brocklyn JR, Thangada S, Liu CH, Hand AR et al. 1998. Sphingosine-1-phosphate as a ligand for the G protein-coupled receptor EDG-1. Science 279:1552–55
     [Google Scholar]
  14. 14. 
    Hishikawa D, Hashidate T, Shimizu T, Shindou H. 2014. Diversity and function of membrane glycerophospholipids generated by the remodeling pathway in mammalian cells. J. Lipid Res. 55:799–807
     [Google Scholar]
  15. 15. 
    Holthuis JC, Menon AK. 2014. Lipid landscapes and pipelines in membrane homeostasis. Nature 510:48–57
     [Google Scholar]
  16. 16. 
    Kobayashi T, Menon AK. 2018. Transbilayer lipid asymmetry. Curr. Biol. 28:R386–91
     [Google Scholar]
  17. 17. 
    Harayama T, Shimizu T. 2020. Roles of polyunsaturated fatty acids, from mediators to membranes. J. Lipid Res. 61:1150–60
     [Google Scholar]
  18. 18. 
    Hossain MS, Mawatari S, Fujino T 2020. Biological functions of plasmalogens. Adv. Exp. Med. Biol. 1299:171–93
     [Google Scholar]
  19. 19. 
    Farooqui AA, Horrocks LA. 2001. Plasmalogens, phospholipase A2, and docosahexaenoic acid turnover in brain tissue. J. Mol. Neurosci. 16:263–72
     [Google Scholar]
  20. 20. 
    Zambelli VO, Picolo G, Fernandes CAH, Fontes MRM, Cury Y. 2017. Secreted phospholipases A2 from animal venoms in pain and analgesia. Toxins 9:406
     [Google Scholar]
  21. 21. 
    Ishii S, Nagase T, Shimizu T. 2002. Platelet-activating factor receptor. Prostaglandins Other Lipid Mediat 68–69:599–609
     [Google Scholar]
  22. 22. 
    Rosen H, Gonzalez-Cabrera PJ, Sanna MG, Brown S. 2009. Sphingosine 1-phosphate receptor signaling. Annu. Rev. Biochem. 78:743–68
     [Google Scholar]
  23. 23. 
    Makide K, Uwamizu A, Shinjo Y, Ishiguro J, Okutani M et al. 2014. Novel lysophospholipid receptors: their structure and function. J. Lipid Res. 55:1986–95
     [Google Scholar]
  24. 24. 
    Pena LA, Fuks Z, Kolesnick R. 1997. Stress-induced apoptosis and the sphingomyelin pathway. Biochem. Pharmacol. 53:615–21
     [Google Scholar]
  25. 25. 
    Venkataraman K, Lee YM, Michaud J, Thangada S, Ai Y et al. 2008. Vascular endothelium as a contributor of plasma sphingosine 1-phosphate. Circ. Res. 102:669–76
     [Google Scholar]
  26. 26. 
    Lee H, Liao JJ, Graeler M, Huang MC, Goetzl EJ. 2002. Lysophospholipid regulation of mononuclear phagocytes. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1582:175–77
     [Google Scholar]
  27. 27. 
    Karliner JS. 2002. Lysophospholipids and the cardiovascular system. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1582:216–21
     [Google Scholar]
  28. 28. 
    Zager RA, Iwata M, Conrad DS, Burkhart KM, Igarashi Y. 1997. Altered ceramide and sphingosine expression during the induction phase of ischemic acute renal failure. Kidney Int 52:60–70
     [Google Scholar]
  29. 29. 
    Troyer DA, Kreisberg JI, Venkatachalam MA. 1986. Lipid alterations in LLC-PK1 cells exposed to mercuric chloride. Kidney Int 29:530–38
     [Google Scholar]
  30. 30. 
    Serhan CN, Gupta SK, Perretti M, Godson C, Brennan E et al. 2020. The atlas of inflammation resolution (AIR). Mol. Aspects Med. 74:100894
     [Google Scholar]
  31. 31. 
    Baeyens A, Fang V, Chen C, Schwab SR. 2015. Exit strategies: S1P signaling and T cell migration. Trends Immunol 36:778–87
     [Google Scholar]
  32. 32. 
    Dixit D, Okuniewska M, Schwab SR. 2019. Secrets and lyase: control of sphingosine 1-phosphate distribution. Immunol. Rev. 289:173–85
     [Google Scholar]
  33. 33. 
    Maceyka M, Spiegel S. 2014. Sphingolipid metabolites in inflammatory disease. Nature 510:58–67
     [Google Scholar]
  34. 34. 
    Lee SC, Dacheux MA, Norman DD, Balazs L, Torres RM et al. 2020. Regulation of tumor immunity by lysophosphatidic acid. Cancers 12:1202
     [Google Scholar]
  35. 35. 
    Suryadevara V, Ramchandran R, Kamp DW, Natarajan V. 2020. Lipid mediators regulate pulmonary fibrosis: potential mechanisms and signaling pathways. Int. J. Mol. Sci. 21:4257
     [Google Scholar]
  36. 36. 
    Ueda H. 2021. Pathogenic mechanisms of lipid mediator lysophosphatidic acid in chronic pain. Prog. Lipid Res. 81:101079
     [Google Scholar]
  37. 37. 
    Frej C, Linder A, Happonen KE, Taylor FB, Lupu F, Dahlbäck B. 2016. Sphingosine 1-phosphate and its carrier apolipoprotein M in human sepsis and in Escherichia coli sepsis in baboons. J. Cell Mol. Med. 20:1170–81
     [Google Scholar]
  38. 38. 
    Olivera A, Eisner C, Kitamura Y, Dillahunt S, Allende L et al. 2010. Sphingosine kinase 1 and sphingosine-1-phosphate receptor 2 are vital to recovery from anaphylactic shock in mice. J. Clin. Investig. 120:1429–40
     [Google Scholar]
  39. 39. 
    Rosen H, Oldstone MBA. 2021. The riddle of the Sphinx: why sphingosine-1-phosphate may help define molecular mechanisms underlying risk stratification for serious COVID-19 infections. EMBO Mol. Med. 13:e13533
     [Google Scholar]
  40. 40. 
    Marfia G, Navone S, Guarnaccia L, Campanella R, Mondoni M et al. 2021. Decreased serum level of sphingosine-1-phosphate: a novel predictor of clinical severity in COVID-19. EMBO Mol. Med. 13:e13424
     [Google Scholar]
  41. 41. 
    Song JW, Lam SM, Fan X, Cao WJ, Wang SY et al. 2020. Omics-driven systems interrogation of metabolic dysregulation in COVID-19 pathogenesis. Cell Metab 32:188–202.e5
     [Google Scholar]
  42. 42. 
    Yanagida K, Masago K, Nakanishi H, Kihara Y, Hamano F et al. 2009. Identification and characterization of a novel lysophosphatidic acid receptor, p2y5/LPA6. J. Biol. Chem. 284:17731–41
     [Google Scholar]
  43. 43. 
    Okudaira M, Inoue A, Shuto A, Nakanaga K, Kano K et al. 2014. Separation and quantification of 2-acyl-1-lysophospholipids and 1-acyl-2-lysophospholipids in biological samples by LC-MS/MS. J. Lipid Res. 55:2178–92
     [Google Scholar]
  44. 44. 
    Lee MJ, Evans M, Hla T. 1996. The inducible G protein-coupled receptor edg-1 signals via the Gi/mitogen-activated protein kinase pathway. J. Biol. Chem. 271:11272–79
     [Google Scholar]
  45. 45. 
    Noguchi K, Ishii S, Shimizu T. 2003. Identification of p2y9/GPR23 as a novel G protein-coupled receptor for lysophosphatidic acid, structurally distant from the Edg family. J. Biol. Chem. 278:25600–6
     [Google Scholar]
  46. 46. 
    Inoue A, Ishiguro J, Kitamura H, Arima N, Okutani M et al. 2012. TGFα shedding assay: an accurate and versatile method for detecting GPCR activation. Nat. Methods 9:1021–29
     [Google Scholar]
  47. 47. 
    Guy AT, Nagatsuka Y, Ooashi N, Inoue M, Nakata A et al. 2015. Glycerophospholipid regulation of modality-specific sensory axon guidance in the spinal cord. Science 349:974–77
     [Google Scholar]
  48. 48. 
    Taniguchi R, Inoue A, Sayama M, Uwamizu A, Yamashita K et al. 2017. Structural insights into ligand recognition by the lysophosphatidic acid receptor LPA6. Nature 548:356–60
     [Google Scholar]
  49. 49. 
    Zhang D, Gao ZG, Zhang K, Kiselev E, Crane S et al. 2015. Two disparate ligand-binding sites in the human P2Y1 receptor. Nature 520:317–21
     [Google Scholar]
  50. 50. 
    Zhang K, Zhang J, Gao ZG, Zhang D, Zhu L et al. 2014. Structure of the human P2Y12 receptor in complex with an antithrombotic drug. Nature 509:115–18
     [Google Scholar]
  51. 51. 
    Nishi T, Kobayashi N, Hisano Y, Kawahara A, Yamaguchi A 2014. Molecular and physiological functions of sphingosine 1-phosphate transporters. Biochim. Biophys. Acta Mol. Cell Biol. Lipids 1841:759–65
     [Google Scholar]
  52. 52. 
    Umezu-Goto M, Kishi Y, Taira A, Hama K, Dohmae N et al. 2002. Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production. J. Cell Biol. 158:227–33
     [Google Scholar]
  53. 53. 
    Tokumura A, Majima E, Kariya Y, Tominaga K, Kogure K et al. 2002. Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase. J. Biol. Chem. 277:39436–42
     [Google Scholar]
  54. 54. 
    Hama K, Aoki J, Fukaya M, Kishi Y, Sakai T et al. 2004. Lysophosphatidic acid and autotaxin stimulate cell motility of neoplastic and non-neoplastic cells through LPA1. J. Biol. Chem. 279:17634–39
     [Google Scholar]
  55. 55. 
    Sonoda H, Aoki J, Hiramatsu T, Ishida M, Bandoh K et al. 2002. A novel phosphatidic acid-selective phospholipase A1 that produces lysophosphatidic acid. J. Biol. Chem. 277:34254–63
     [Google Scholar]
  56. 56. 
    Bathena SP, Huang J, Nunn ME, Miyamoto T, Parrish LC et al. 2011. Quantitative determination of lysophosphatidic acids (LPAs) in human saliva and gingival crevicular fluid (GCF) by LC-MS/MS. J. Pharm. Biomed. Anal. 56:402–7
     [Google Scholar]
  57. 57. 
    Kuwajima K, Sumitani M, Kurano M, Kano K, Nishikawa M et al. 2018. Lysophosphatidic acid is associated with neuropathic pain intensity in humans: an exploratory study. PLOS ONE 13:e0207310
     [Google Scholar]
  58. 58. 
    Tanaka M, Kishi Y, Takanezawa Y, Kakehi Y, Aoki J, Arai H. 2004. Prostatic acid phosphatase degrades lysophosphatidic acid in seminal plasma. FEBS Lett 571:197–204
     [Google Scholar]
  59. 59. 
    Aoki J, Taira A, Takanezawa Y, Kishi Y, Hama K et al. 2002. Serum lysophosphatidic acid is produced through diverse phospholipase pathways. J. Biol. Chem. 277:48737–44
     [Google Scholar]
  60. 60. 
    Brindley DN, Pilquil C. 2009. Lipid phosphate phosphatases and signaling. J. Lipid Res. 50:Suppl.S225–30
     [Google Scholar]
  61. 61. 
    Hama K, Bandoh K, Kakehi Y, Aoki J, Arai H. 2002. Lysophosphatidic acid (LPA) receptors are activated differentially by biological fluids: possible role of LPA-binding proteins in activation of LPA receptors. FEBS Lett 523:187–92
     [Google Scholar]
  62. 62. 
    Sugiura T, Nakane S, Kishimoto S, Waku K, Yoshioka Y, Tokumura A. 2002. Lysophosphatidic acid, a growth factor-like lipid, in the saliva. J. Lipid Res. 43:2049–55
     [Google Scholar]
  63. 63. 
    Yatomi Y, Kurano M, Ikeda H, Igarashi K, Kano K, Aoki J 2018. Lysophospholipids in laboratory medicine. Proc. Jpn. Acad. Ser. B Phys. Biol. Sci. 94:373–89
     [Google Scholar]
  64. 64. 
    Abdul Rahman M, Mohamad Haron DE, Hollows RJ, Abdul Ghani ZDF, Ali Mohd M et al. 2020. Profiling lysophosphatidic acid levels in plasma from head and neck cancer patients. PeerJ 8:e9304
     [Google Scholar]
  65. 65. 
    Bese T, Barbaros M, Baykara E, Guralp O, Cengiz S et al. 2010. Comparison of total plasma lysophosphatidic acid and serum CA-125 as a tumor marker in the diagnosis and follow-up of patients with epithelial ovarian cancer. J. Gynecol. Oncol. 21:248–54
     [Google Scholar]
  66. 66. 
    Watanabe N, Ikeda H, Nakamura K, Ohkawa R, Kume Y et al. 2007. Plasma lysophosphatidic acid level and serum autotaxin activity are increased in liver injury in rats in relation to its severity. Life Sci 81:1009–15
     [Google Scholar]
  67. 67. 
    Dohi T, Miyauchi K, Ohkawa R, Nakamura K, Kishimoto T et al. 2012. Increased circulating plasma lysophosphatidic acid in patients with acute coronary syndrome. Clin. Chim. Acta 413:207–12
     [Google Scholar]
  68. 68. 
    Kurano M, Suzuki A, Inoue A, Tokuhara Y, Kano K et al. 2015. Possible involvement of minor lysophospholipids in the increase in plasma lysophosphatidic acid in acute coronary syndrome. Arterioscler. Thromb. Vasc. Biol. 35:463–70
     [Google Scholar]
  69. 69. 
    Xu Y, Shen Z, Wiper DW, Wu M, Morton RE et al. 1998. Lysophosphatidic acid as a potential biomarker for ovarian and other gynecologic cancers. JAMA 280:719–23
     [Google Scholar]
  70. 70. 
    Onorato JM, Shipkova P, Minnich A, Aubry AF, Easter J, Tymiak A 2014. Challenges in accurate quantitation of lysophosphatidic acids in human biofluids. J. Lipid Res. 55:1784–96
     [Google Scholar]
  71. 71. 
    Nakamura K, Kishimoto T, Ohkawa R, Okubo S, Tozuka M et al. 2007. Suppression of lysophosphatidic acid and lysophosphatidylcholine formation in the plasma in vitro: proposal of a plasma sample preparation method for laboratory testing of these lipids. Anal. Biochem. 367:20–27
     [Google Scholar]
  72. 72. 
    Yagi T, Kuschner CE, Shoaib M, Choudhary RC, Becker LB et al. 2019. Relative ratios enhance the diagnostic power of phospholipids in distinguishing benign and cancerous ovarian masses. Cancers 12:72
     [Google Scholar]
  73. 73. 
    Kano K, Matsumoto H, Kono N, Kurano M, Yatomi Y, Aoki J 2021. Suppressing postcollection lysophosphatidic acid metabolism improves the precision of plasma LPA quantification. J. Lipid Res. 62:100029
     [Google Scholar]
  74. 74. 
    Hammad SM, Pierce JS, Soodavar F, Smith KJ, Al Gadban MM et al. 2010. Blood sphingolipidomics in healthy humans: impact of sample collection methodology. J. Lipid Res. 51:3074–87
     [Google Scholar]
  75. 75. 
    Uranbileg B, Ito N, Kurano M, Saigusa D, Saito R et al. 2019. Alteration of the lysophosphatidic acid and its precursor lysophosphatidylcholine levels in spinal cord stenosis: a study using a rat cauda equina compression model. Sci. Rep. 9:16578
     [Google Scholar]
  76. 76. 
    Black KE, Berdyshev E, Bain G, Castelino FV, Shea BS et al. 2016. Autotaxin activity increases locally following lung injury, but is not required for pulmonary lysophosphatidic acid production or fibrosis. FASEB J 30:2435–50
     [Google Scholar]
  77. 77. 
    Lee C-W, Rivera R, Gardell S, Dubin AE, Chun J. 2006. GPR92 as a new G12/13- and Gq-coupled lysophosphatidic acid receptor that increases cAMP, LPA5. J. Biol. Chem. 281:23589–97
     [Google Scholar]
  78. 78. 
    Jones SM, Kazlauskas A. 2001. Growth-factor-dependent mitogenesis requires two distinct phases of signalling. Nat. Cell Biol. 3:165–72
     [Google Scholar]
  79. 79. 
    Stracke ML, Krutzsch HC, Unsworth EJ, Årestad A, Cioce V et al. 1992. Identification, purification, and partial sequence analysis of autotaxin, a novel motility-stimulating protein. J. Biol. Chem. 267:2524–29
     [Google Scholar]
  80. 80. 
    Llona-Minguez S, Ghassemian A, Helleday T 2015. Lysophosphatidic acid receptor (LPAR) modulators: the current pharmacological toolbox. Prog. Lipid Res. 58:51–75
     [Google Scholar]
  81. 81. 
    Fukushima N, Furuta D, Tsujiuchi T 2011. Coordinated interactions between actin and microtubules through crosslinkers in neurite retraction induced by lysophosphatidic acid. Neurochem. Int. 59:109–13
     [Google Scholar]
  82. 82. 
    Tager AM, LaCamera P, Shea BS, Campanella GS, Selman M et al. 2008. The lysophosphatidic acid receptor LPA1 links pulmonary fibrosis to lung injury by mediating fibroblast recruitment and vascular leak. Nat. Med. 14:45–54
     [Google Scholar]
  83. 83. 
    Huang LS, Fu P, Patel P, Harijith A, Sun T et al. 2013. Lysophosphatidic acid receptor-2 deficiency confers protection against bleomycin-induced lung injury and fibrosis in mice. Am. J. Respir. Cell Mol. Biol. 49:912–22
     [Google Scholar]
  84. 84. 
    Sakai N, Chun J, Duffield JS, Lagares D, Wada T et al. 2017. Lysophosphatidic acid signaling through its receptor initiates profibrotic epithelial cell fibroblast communication mediated by epithelial cell derived connective tissue growth factor. Kidney Int 91:628–41
     [Google Scholar]
  85. 85. 
    Castelino FV, Seiders J, Bain G, Brooks SF, King CD et al. 2011. Amelioration of dermal fibrosis by genetic deletion or pharmacologic antagonism of lysophosphatidic acid receptor 1 in a mouse model of scleroderma. Arthritis Rheum 63:1405–15
     [Google Scholar]
  86. 86. 
    Nishioka T, Arima N, Kano K, Hama K, Itai E et al. 2016. ATX-LPA1 axis contributes to proliferation of chondrocytes by regulating fibronectin assembly leading to proper cartilage formation. Sci. Rep. 6:23433
     [Google Scholar]
  87. 87. 
    Ninou I, Kaffe E, Müller S, Budd DC, Stevenson CS et al. 2018. Pharmacologic targeting of the ATX/LPA axis attenuates bleomycin-induced pulmonary fibrosis. Pulm. Pharmacol. Ther. 52:32–40
     [Google Scholar]
  88. 88. 
    Maher TM, van der Aar EM, Van de Steen O, Allamassey L, Desrivot J et al. 2018. Safety, tolerability, pharmacokinetics, and pharmacodynamics of GLPG1690, a novel autotaxin inhibitor, to treat idiopathic pulmonary fibrosis (FLORA): a phase 2a randomised placebo-controlled trial. Lancet Respir. Med. 6:627–35
     [Google Scholar]
  89. 89. 
    Inoue M, Rashid MH, Fujita R, Contos JJ, Chun J, Ueda H 2004. Initiation of neuropathic pain requires lysophosphatidic acid receptor signaling. Nat. Med. 10:712–18
     [Google Scholar]
  90. 90. 
    Hall SM. 1972. The effect of injections of lysophosphatidyl choline into white matter of the adult mouse spinal cord. J. Cell Sci. 10:535–46
     [Google Scholar]
  91. 91. 
    Hayakawa K, Kurano M, Ohya J, Oichi T, Kano K et al. 2019. Lysophosphatidic acids and their substrate lysophospholipids in cerebrospinal fluid as objective biomarkers for evaluating the severity of lumbar spinal stenosis. Sci. Rep. 9:9144
     [Google Scholar]
  92. 92. 
    Tanaka M, Okudaira S, Kishi Y, Ohkawa R, Iseki S et al. 2006. Autotaxin stabilizes blood vessels and is required for embryonic vasculature by producing lysophosphatidic acid. J. Biol. Chem. 281:25822–30
     [Google Scholar]
  93. 93. 
    Offermanns S, Mancino V, Revel JP, Simon MI. 1997. Vascular system defects and impaired cell chemokinesis as a result of Gα13 deficiency. Science 275:533–36
     [Google Scholar]
  94. 94. 
    Ruppel KM, Willison D, Kataoka H, Wang A, Zheng Y-W et al. 2005. Essential role for Gα13 in endothelial cells during embryonic development. PNAS 102:8281–86
     [Google Scholar]
  95. 95. 
    Sumida H, Noguchi K, Kihara Y, Abe M, Yanagida K et al. 2010. LPA4 regulates blood and lymphatic vessel formation during mouse embryogenesis. Blood 116:5060–70
     [Google Scholar]
  96. 96. 
    Jain RK. 2001. Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat. Med. 7:987–89
     [Google Scholar]
  97. 97. 
    Takara K, Eino D, Ando K, Yasuda D, Naito H et al. 2017. Lysophosphatidic acid receptor 4 activation augments drug delivery in tumors by tightening endothelial cell-cell contact. Cell Rep 20:2072–86
     [Google Scholar]
  98. 98. 
    Ye X, Hama K, Contos JJ, Anliker B, Inoue A et al. 2005. LPA3-mediated lysophosphatidic acid signalling in embryo implantation and spacing. Nature 435:104–8
     [Google Scholar]
  99. 99. 
    Aikawa S, Kano K, Inoue A, Wang J, Saigusa D et al. 2017. Autotaxin–lysophosphatidic acid–LPA3 signaling at the embryo-epithelial boundary controls decidualization pathways. EMBO J 36:2146–60
     [Google Scholar]
  100. 100. 
    Arosh JA, Lee J, Balasubbramanian D, Stanley JA, Long CR et al. 2015. Molecular and preclinical basis to inhibit PGE2 receptors EP2 and EP4 as a novel nonsteroidal therapy for endometriosis. PNAS 112:9716–21
     [Google Scholar]
  101. 101. 
    Ferrandina G, Ranelletti FO, Lauriola L, Fanfani F, Legge F et al. 2002. Cyclooxygenase-2 (COX-2), epidermal growth factor receptor (EGFR), and Her-2/neu expression in ovarian cancer. Gynecol. Oncol. 85:305–10
     [Google Scholar]
  102. 102. 
    Levin ER. 2003. Bidirectional signaling between the estrogen receptor and the epidermal growth factor receptor. Mol. Endocrinol. 17:309–17
     [Google Scholar]
  103. 103. 
    Miller MA, Moss ML, Powell G, Petrovich R, Edwards L et al. 2015. Targeting autocrine HB-EGF signaling with specific ADAM12 inhibition using recombinant ADAM12 prodomain. Sci. Rep. 5:15150
     [Google Scholar]
  104. 104. 
    Ota H, Igarashi S, Sasaki M, Tanaka T. 2001. Distribution of cyclooxygenase-2 in eutopic and ectopic endometrium in endometriosis and adenomyosis. Hum. Reprod. 16:561–66
     [Google Scholar]
  105. 105. 
    Zong Y, Huang J, Sankarasharma D, Morikawa T, Fukayama M et al. 2012. Stromal epigenetic dysregulation is sufficient to initiate mouse prostate cancer via paracrine Wnt signaling. PNAS 109:E3395–404
     [Google Scholar]
  106. 106. 
    Contos JJ, Fukushima N, Weiner JA, Kaushal D, Chun J 2000. Requirement for the lpA1 lysophosphatidic acid receptor gene in normal suckling behavior. PNAS 97:13384–89
     [Google Scholar]
  107. 107. 
    Harrison SM, Reavill C, Brown G, Brown JT, Cluderay JE et al. 2003. LPA1 receptor-deficient mice have phenotypic changes observed in psychiatric disease. Mol. Cell Neurosci. 24:1170–79
     [Google Scholar]
  108. 108. 
    Kingsbury MA, Rehen SK, Contos JJ, Higgins CM, Chun J 2003. Non-proliferative effects of lysophosphatidic acid enhance cortical growth and folding. Nat. Neurosci. 6:1292–99
     [Google Scholar]
  109. 109. 
    Yung YC, Mutoh T, Lin ME, Noguchi K, Rivera RR et al. 2011. Lysophosphatidic acid signaling may initiate fetal hydrocephalus. Sci. Transl. Med. 3:99ra87
     [Google Scholar]
  110. 110. 
    Kanda H, Newton R, Klein R, Morita Y, Gunn MD, Rosen SD. 2008. Autotaxin, an ectoenzyme that produces lysophosphatidic acid, promotes the entry of lymphocytes into secondary lymphoid organs. Nat. Immunol. 9:415–23
     [Google Scholar]
  111. 111. 
    Nakasaki T, Tanaka T, Okudaira S, Hirosawa M, Umemoto E et al. 2008. Involvement of the lysophosphatidic acid-generating enzyme autotaxin in lymphocyte-endothelial cell interactions. Am. J. Pathol. 173:1566–76
     [Google Scholar]
  112. 112. 
    Hata E, Sasaki N, Takeda A, Tohya K, Umemoto E et al. 2016. Lysophosphatidic acid receptors LPA4 and LPA6 differentially promote lymphocyte transmigration across high endothelial venules in lymph nodes. Int. Immunol. 28:283–92
     [Google Scholar]
  113. 113. 
    Takeda A, Kobayashi D, Aoi K, Sasaki N, Sugiura Y et al. 2016. Fibroblastic reticular cell-derived lysophosphatidic acid regulates confined intranodal T-cell motility. eLife 5:e10561
     [Google Scholar]
  114. 114. 
    Kazantseva A, Goltsov A, Zinchenko R, Grigorenko AP, Abrukova AV et al. 2006. Human hair growth deficiency is linked to a genetic defect in the phospholipase gene LIPH. Science 314:982–85
     [Google Scholar]
  115. 115. 
    Mehmood S, Jan A, Raza SI, Ahmad F, Younus M et al. 2016. Disease causing homozygous variants in the human hairless gene. Int. J. Dermatol. 55:977–81
     [Google Scholar]
  116. 116. 
    Shimomura Y, Ito M, Christiano AM. 2009. Mutations in the LIPH gene in three Japanese families with autosomal recessive woolly hair/hypotrichosis. J. Dermatol. Sci. 56:205–7
     [Google Scholar]
  117. 117. 
    Pasternack SM, von Kugelgen I, Al Aboud K, Lee YA, Ruschendorf F et al. 2008. G protein-coupled receptor P2Y5 and its ligand LPA are involved in maintenance of human hair growth. Nat. Genet. 40:329–34
     [Google Scholar]
  118. 118. 
    Shimomura Y, Wajid M, Ishii Y, Shapiro L, Petukhova L et al. 2008. Disruption of P2RY5, an orphan G protein-coupled receptor, underlies autosomal recessive woolly hair. Nat. Genet. 40:335–39
     [Google Scholar]
  119. 119. 
    Diribarne M, Mata X, Chantry-Darmon C, Vaiman A, Auvinet G et al. 2011. A deletion in exon 9 of the LIPH gene is responsible for the rex hair coat phenotype in rabbits (Oryctolagus cuniculus). PLOS ONE 6:e19281
     [Google Scholar]
  120. 120. 
    Inoue A, Arima N, Ishiguro J, Prestwich GD, Arai H, Aoki J. 2011. LPA-producing enzyme PA-PLA1α regulates hair follicle development by modulating EGFR signalling. EMBO J 30:4248–60
     [Google Scholar]
  121. 121. 
    Blaydon DC, Biancheri P, Di W-L, Plagnol V, Cabral RM et al. 2011. Inflammatory skin and bowel disease linked to ADAM17 deletion. N. Engl. J. Med. 365:1502–8
     [Google Scholar]
  122. 122. 
    Engelbrecht E, Levesque MV, He L, Vanlandewijck M, Nitzsche A et al. 2020. Sphingosine 1-phosphate-regulated transcriptomes in heterogenous arterial and lymphatic endothelium of the aorta. eLife 9:e52690
     [Google Scholar]
  123. 123. 
    Yanagida K, Engelbrecht E, Niaudet C, Jung B, Gaengel K et al. 2020. Sphingosine 1-phosphate receptor signaling establishes AP-1 gradients to allow for retinal endothelial cell specialization. Dev. Cell 52:779–93.e7
     [Google Scholar]
  124. 124. 
    Jung B, Obinata H, Galvani S, Mendelson K, Ding BS et al. 2012. Flow-regulated endothelial S1P receptor-1 signaling sustains vascular development. Dev. Cell 23:600–10
     [Google Scholar]
  125. 125. 
    Schumacher L. 2019. Collective cell migration in development. Adv. Exp. Med. Biol. 1146:105–16
     [Google Scholar]
  126. 126. 
    Gudipaty SA, Rosenblatt J. 2017. Epithelial cell extrusion: pathways and pathologies. Semin. Cell Dev. Biol. 67:132–40
     [Google Scholar]
  127. 127. 
    Duszyc K, Gomez GA, Lagendijk AK, Yau M-K, Nanavati BN et al. 2021. Mechanotransduction activates RhoA in the neighbors of apoptotic epithelial cells to engage apical extrusion. Curr. Biol. 31:1326–36.e5
     [Google Scholar]
  128. 128. 
    Mendelson K, Pandey S, Hisano Y, Carellini F, Das BC et al. 2017. The ceramide synthase 2b gene mediates genomic sensing and regulation of sphingosine levels during zebrafish embryogenesis. eLife 6:e21992
     [Google Scholar]
  129. 129. 
    Fukui H, Fukuhara S, Mochizuki N 2016. S1P-S1p2 signaling in cardiac precursor cells migration. Etiology and Morphogenesis of Congenital Heart Disease: From Gene Function and Cellular Interaction to Morphology T Nakanishi, RR Markwald, HS Baldwin, BB Keller, D Srivastava, H Yamagishi 125–26 Tokyo: Springer Japan
     [Google Scholar]
  130. 130. 
    Mendoza A, Fang V, Chen C, Serasinghe M, Verma A et al. 2017. Lymphatic endothelial S1P promotes mitochondrial function and survival in naive T cells. Nature 546:158–61
     [Google Scholar]
  131. 131. 
    Fransen MF, Schoonderwoerd M, Knopf P, Camps MG, Hawinkels LJ et al. 2018. Tumor-draining lymph nodes are pivotal in PD-1/PD-L1 checkpoint therapy. JCI Insight 3:e124507
     [Google Scholar]
  132. 132. 
    Chakraborty P, Vaena SG, Thyagarajan K, Chatterjee S, Al-Khami A et al. 2019. Pro-survival lipid sphingosine-1-phosphate metabolically programs T cells to limit anti-tumor activity. Cell Rep 28:1879–93.e7
     [Google Scholar]
  133. 133. 
    Onishi H, Kiyota A, Koya N, Tanaka H, Umebayashi M et al. 2014. Random migration contributes to cytotoxicity of activated CD8+ T-lymphocytes but not NK cells. Anticancer Res 34:3947–56
     [Google Scholar]
  134. 134. 
    Rathinasamy A, Domschke C, Ge Y, Bohm HH, Dettling S et al. 2017. Tumor specific regulatory T cells in the bone marrow of breast cancer patients selectively upregulate the emigration receptor S1P1. Cancer Immunol. Immunother. 66:593–603
     [Google Scholar]
  135. 135. 
    Chongsathidkiet P, Jackson C, Koyama S, Loebel F, Cui X et al. 2018. Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors. Nat. Med. 24:1459–68
     [Google Scholar]
  136. 136. 
    Masuda A, Fujii T, Iwasawa Y, Nakamura K, Ohkawa R et al. 2011. Serum autotaxin measurements in pregnant women: application for the differentiation of normal pregnancy and pregnancy-induced hypertension. Clin. Chim. Acta 412:1944–50
     [Google Scholar]
  137. 137. 
    Tokumura A, Kanaya Y, Miyake M, Yamano S, Irahara M, Fukuzawa K. 2002. Increased production of bioactive lysophosphatidic acid by serum lysophospholipase D in human pregnancy. Biol. Reprod. 67:1386–92
     [Google Scholar]
  138. 138. 
    Ikeda H, Yatomi Y. 2012. Autotaxin in liver fibrosis. Clin. Chim. Acta 413:1817–21
     [Google Scholar]
  139. 139. 
    Masuda A, Nakamura K, Izutsu K, Igarashi K, Ohkawa R et al. 2008. Serum autotaxin measurement in haematological malignancies: a promising marker for follicular lymphoma. Br. J. Haematol. 143:60–70
     [Google Scholar]
  140. 140. 
    Shao X, Uojima H, Setsu T, Okubo T, Atsukawa M et al. 2020. Usefulness of autotaxin for the complications of liver cirrhosis. World J. Gastroenterol. 26:97–108
     [Google Scholar]
  141. 141. 
    Jiang G, Inoue A, Aoki J, Prestwich GD. 2013. Phosphorothioate analogs of sn-2 radyl lysophosphatidic acid (LPA): metabolically stabilized LPA receptor agonists. Bioorg. Med. Chem. Lett. 23:1865–69
     [Google Scholar]
  142. 142. 
    Kano K, Arima N, Ohgami M, Aoki J. 2008. LPA and its analogs-attractive tools for elucidation of LPA biology and drug development. Curr. Med. Chem. 15:2122–31
     [Google Scholar]
  143. 143. 
    Kuo B, Szabó E, Lee SC, Balogh A, Norman D et al. 2018. The LPA2 receptor agonist Radioprotectin-1 spares Lgr5-positive intestinal stem cells from radiation injury in murine enteroids. Cell Signal 51:23–33
     [Google Scholar]
  144. 144. 
    Parrill AL. 2014. Design of anticancer lysophosphatidic acid agonists and antagonists. Future Med. Chem. 6:871–83
     [Google Scholar]
  145. 145. 
    Matralis AN, Afantitis A, Aidinis V 2019. Development and therapeutic potential of autotaxin small molecule inhibitors: from bench to advanced clinical trials. Med. Res. Rev. 39:976–1013
     [Google Scholar]
  146. 146. 
    Salgado-Polo F, Perrakis A. 2019. The structural binding mode of the four autotaxin inhibitor types that differentially affect catalytic and non-catalytic functions. Cancers 11:1577
     [Google Scholar]
  147. 147. 
    Nitzsche A, Poittevin M, Benarab A, Bonnin P, Faraco G et al. 2021. Endothelial S1P1 signaling counteracts infarct expansion in ischemic stroke. Circ. Res. 128:3363–82
     [Google Scholar]
  148. 148. 
    Kittaka H, Uchida K, Fukuta N, Tominaga M. 2017. Lysophosphatidic acid-induced itch is mediated by signalling of LPA5 receptor, phospholipase D and TRPA1/TRPV1. J. Physiol. 595:2681–98
     [Google Scholar]
  149. 149. 
    McIntyre TM, Pontsler AV, Silva AR, St Hilaire A, Xu Y et al. 2003. Identification of an intracellular receptor for lysophosphatidic acid (LPA): LPA is a transcellular PPARγ agonist. PNAS 100:131–36
     [Google Scholar]
  150. 150. 
    Fang V, Chaluvadi VS, Ramos-Perez WD, Mendoza A, Baeyens A et al. 2017. Gradients of the signaling lipid S1P in lymph nodes position natural killer cells and regulate their interferon-γ response. Nat. Immunol. 18:15–25
     [Google Scholar]
  151. 151. 
    Ramos-Perez WD, Fang V, Escalante-Alcalde D, Cammer M, Schwab SR. 2015. A map of the distribution of sphingosine 1-phosphate in the spleen. Nat. Immunol. 16:1245–52
     [Google Scholar]
  152. 152. 
    Sarkisyan G, Gay LJ, Nguyen N, Felding BH, Rosen H. 2014. Host endothelial S1PR1 regulation of vascular permeability modulates tumor growth. Am. J. Physiol. Cell Physiol. 307:C14–24
     [Google Scholar]
  153. 153. 
    Kono M, Conlon EG, Lux SY, Yanagida K, Hla T, Proia RL. 2017. Bioluminescence imaging of G protein-coupled receptor activation in living mice. Nat. Commun. 8:1163
     [Google Scholar]
  154. 154. 
    Kono M, Tucker AE, Tran J, Bergner JB, Turner EM, Proia RL 2014. Sphingosine-1-phosphate receptor 1 reporter mice reveal receptor activation sites in vivo. J. Clin. Investig. 124:2076–86
     [Google Scholar]
  155. 155. 
    Nitzsche A, Poittevin M, Benarab A, Bonnin P, Faraco G et al. 2021. Endothelial S1P1 signaling counteracts infarct expansion in ischemic stroke. Circ. Res. 128:363–82
     [Google Scholar]
  156. 156. 
    Wang J, Kano K, Saigusa D, Aoki J. 2019. Measurement of the spatial distribution of S1P in small quantities of tissues: development and application of a highly sensitive LC-MS/MS method combined with laser microdissection. Mass Spectrom 8:A0072
     [Google Scholar]
  157. 157. 
    Iwama T, Kano K, Saigusa D, Ekroos K, van Echten-Deckert G et al. 2021. Development of an on-tissue derivatization method for MALDI mass spectrometry imaging of bioactive lipids containing phosphate monoester using Phos-tag. Anal. Chem. 93:3867–75
     [Google Scholar]
/content/journals/10.1146/annurev-pathol-050420-025929
Loading
Lysophospholipid Mediators in Health and Disease
Annual Review of Pathology: Mechanisms of Disease 17, 459 (2022); https://doi.org/10.1146/annurev-pathol-050420-025929
/content/journals/10.1146/annurev-pathol-050420-025929
/content/journals/10.1146/annurev-pathol-050420-025929
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error