Vascular Permeability in Idiopathic Pulmonary Fibrosis: Comparison
View Latest Version
Please note this is a comparison between Version 1 by Girish Vinayak Jayant and Version 6 by Rita Xu.

Idiopathic pulmonary fibrosis (IPF) is a disease that causes scarring and fibrotic transformation of the lung parenchyma, resulting in the progressive loss of respiratory function and, often, death. An increasing body of literature shows that pulmonary vascular permeability may play a big role in the pathogenesis of this condition. There is a search for therapeutic targets to try and modulate this vascular permeability in fibrotic lungs. One such class of targets that shows great promise is sphingolipids.

Idiopathic pulmonary fibrosis (IPF) is a disease that causes scarring and fibrotic transformation of the lung parenchyma, resulting in the progressive loss of respiratory function and, often, death. An increasing body of literature shows that pulmonary vascular permeability may play a big role in the pathogenesis of this condition. There is a search for therapeutic targets to try and modulate this vascular permeability in fibrotic lungs. One such class of targets that shows great promise is sphingolipids. In this review, we examine the ways that sphingolipids can affect vascular permeability and the pathogenesis of IPF, as well as the pros and cons of their potential role as therapeutic targets for treating IPF. 

  • idiopathic pulmonary fibrosis
  • sphingolipids
  • sphingosine-1-phosphate
Please wait, diff process is still running!

References

  1. Zheng Q, Cox IA, Campbell JA, et al. Mortality and survival in idiopathic pulmonary fibrosis: a systematic review and meta-analysis. ERJ Open Res. 2022;8(1):00591-02021. doi:10.1183/23120541.00591-2021Maher, T.M.; Bendstrup, E.; Dron, L.; Langley, J.; Smith, G.; Khalid, J.M.; Patel, H.; Kreuter, M. Global incidence and prevalence of idiopathic pulmonary fibrosis. Respir. Res. 2021, 22, 197.
  2. Nathan SD, Albera C, Bradford WZ, et al. Effect of pirfenidone on mortality: pooled analyses and meta-analyses of clinical trials in idiopathic pulmonary fibrosis. Lancet Respir Med. 2017;5(1):33-41. doi:10.1016/S2213-2600(16)30326-5Zheng, Q.; Cox, I.A.; Campbell, J.A.; Xia, Q.; Otahal, P.; de Graaff, B.; Corte, T.J.; Teoh, A.K.Y.; Walters, E.H.; Palmer, A.J. Mortality and survival in idiopathic pulmonary fibrosis: A systematic review and meta-analysis. ERJ Open Res. 2022, 8, 00591–2021.
  3. Spagnolo P, Kropski JA, Jones MG, et al. Idiopathic pulmonary fibrosis: Disease mechanisms and drug development. Pharmacol Ther. 2021;222:107798. doi:10.1016/j.pharmthera.2020.107798Nathan, S.D.; Albera, C.; Bradford, W.Z.; Costabel, U.; Glaspole, I.; Glassberg, M.K.; Kardatzke, D.R.; Daigl, M.; Kirchgaessler, K.-U.; Lancaster, L.H.; et al. Effect of pirfenidone on mortality: Pooled analyses and meta-analyses of clinical trials in idiopathic pulmonary fibrosis. Lancet Respir. Med. 2017, 5, 33–41.
  4. Noble PW, Albera C, Bradford WZ, et al. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials. Lancet Lond Engl. 2011;377(9779):1760-1769. doi:10.1016/S0140-6736(11)60405-4Spagnolo, P.; Kropski, J.A.; Jones, M.G.; Lee, J.S.; Rossi, G.; Karampitsakos, T.; Maher, T.M.; Tzouvelekis, A.; Ryerson, C.J. Idiopathic pulmonary fibrosis: Disease mechanisms and drug development. Pharmacol. Ther. 2021, 222, 107798.
  5. Taniguchi H, Ebina M, Kondoh Y, et al. Pirfenidone in idiopathic pulmonary fibrosis. Eur Respir J. 2010;35(4):821-829. doi:10.1183/09031936.00005209Noble, P.W.; Albera, C.; Bradford, W.Z.; Costabel, U.; Glassberg, M.K.; Kardatzke, D.; King, T.E.; Lancaster, L.; Sahn, S.A.; Szwarcberg, J.; et al. Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): Two randomised trials. Lancet 2011, 377, 1760–1769.
  6. Canestaro WJ, Forrester SH, Raghu G, Ho L, Devine BE. Drug Treatment of Idiopathic Pulmonary Fibrosis: Systematic Review and Network Meta-Analysis. Chest. 2016;149(3):756-766. doi:10.1016/j.chest.2015.11.013Taniguchi, H.; Ebina, M.; Kondoh, Y.; Ogura, T.; Azuma, A.; Suga, M.; Taguchi, Y.; Takahashi, H.; Nakata, K.; Sato, A.; et al. Pirfenidone in idiopathic pulmonary fibrosis. Eur. Respir. J. 2010, 35, 821–829.
  7. Ahluwalia N, Shea BS, Tager AM. New therapeutic targets in idiopathic pulmonary fibrosis. Aiming to rein in runaway wound-healing responses. Am J Respir Crit Care Med. 2014;190(8):867-878. doi:10.1164/rccm.201403-0509PPCanestaro, W.J.; Forrester, S.H.; Raghu, G.; Ho, L.; Devine, B.E. Drug Treatment of Idiopathic Pulmonary Fibrosis: Systematic Review and Network Meta-Analysis. Chest 2016, 149, 756–766.
  8. Hewlett JC, Kropski JA, Blackwell TS. Idiopathic pulmonary fibrosis: Epithelial-mesenchymal interactions and emerging therapeutic targets. Matrix Biol J Int Soc Matrix Biol. 2018;71-72:112-127. doi:10.1016/j.matbio.2018.03.021Ahluwalia, N.; Shea, B.S.; Tager, A.M. New therapeutic targets in idiopathic pulmonary fibrosis. Aiming to rein in runaway wound-healing responses. Am. J. Respir. Crit. Care Med. 2014, 190, 867–878.
  9. Yang J, Pan X, Wang L, Yu G. Alveolar cells under mechanical stressed niche: critical contributors to pulmonary fibrosis. Mol Med Camb Mass. 2020;26(1):95. doi:10.1186/s10020-020-00223-wYang, J.; Pan, X.; Wang, L.; Yu, G. Alveolar cells under mechanical stressed niche: Critical contributors to pulmonary fibrosis. Mol. Med. 2020, 26, 95.
  10. McKeown S, Richter AG, O’Kane C, McAuley DF, Thickett DR. MMP expression and abnormal lung permeability are important determinants of outcome in IPF. Eur Respir J. 2009;33(1):77-84. doi:10.1183/09031936.00060708Hewlett, J.C.; Kropski, J.A.; Blackwell, T.S. Idiopathic pulmonary fibrosis: Epithelial-mesenchymal interactions and emerging therapeutic targets. Matrix Biol. 2018, 71–72, 112–127.
  11. Declercq M, Treps L, Carmeliet P, Witters P. The role of endothelial cells in cystic fibrosis. J Cyst Fibros Off J Eur Cyst Fibros Soc. 2019;18(6):752-761. doi:10.1016/j.jcf.2019.07.005McKeown, S.; Richter, A.G.; O’Kane, C.; McAuley, D.F.; Thickett, D.R. MMP expression and abnormal lung permeability are important determinants of outcome in IPF. Eur. Respir. J. 2009, 33, 77–84.
  12. Murakami A, Takasugi H, Ohnuma S, et al. Sphingosine 1-phosphate (S1P) regulates vascular contraction via S1P3 receptor: investigation based on a new S1P3 receptor antagonist. Mol Pharmacol. 2010;77(4):704-713. doi:10.1124/mol.109.061481Declercq, M.; Treps, L.; Carmeliet, P.; Witters, P. The role of endothelial cells in cystic fibrosis. J. Cyst. Fibros. 2019, 18, 752–761.
  13. Huang LS, Sudhadevi T, Fu P, et al. Sphingosine Kinase 1/S1P Signaling Contributes to Pulmonary Fibrosis by Activating Hippo/YAP Pathway and Mitochondrial Reactive Oxygen Species in Lung Fibroblasts. Int J Mol Sci. 2020;21(6):2064. doi:10.3390/ijms21062064Murakami, A.; Takasugi, H.; Ohnuma, S.; Koide, Y.; Sakurai, A.; Takeda, S.; Hasegawa, T.; Sasamori, J.; Konno, T.; Hayashi, K.; et al. Sphingosine 1-phosphate (S1P) regulates vascular contraction via S1P3 receptor: Investigation based on a new S1P3 receptor antagonist. Mol. Pharmacol. 2010, 77, 704–713.
  14. Khan SA, Goliwas KF, Deshane JS. Sphingolipids in Lung Pathology in the Coronavirus Disease Era: A Review of Sphingolipid Involvement in the Pathogenesis of Lung Damage. Front Physiol. 2021;12:760638. doi:10.3389/fphys.2021.760638Huang, L.S.; Sudhadevi, T.; Fu, P.; Punathil-Kannan, P.-K.; Ebenezer, D.L.; Ramchandran, R.; Putherickal, V.; Cheresh, P.; Zhou, G.; Ha, A.W.; et al. Sphingosine Kinase 1/S1P Signaling Contributes to Pulmonary Fibrosis by Activating Hippo/YAP Pathway and Mitochondrial Reactive Oxygen Species in Lung Fibroblasts. Int. J. Mol. Sci. 2020, 21, 2064.
  15. Jernigan PL, Makley AT, Hoehn RS, Edwards MJ, Pritts TA. The role of sphingolipids in endothelial barrier function. Biol Chem. 2015;396(6-7):681-691. doi:10.1515/hsz-2014-0305Khan, S.A.; Goliwas, K.F.; Deshane, J.S. Sphingolipids in Lung Pathology in the Coronavirus Disease Era: A Review of Sphingolipid Involvement in the Pathogenesis of Lung Damage. Front. Physiol. 2021, 12, 760638.
  16. Kuperberg SJ, Wadgaonkar R. Sepsis-Associated Encephalopathy: The Blood-Brain Barrier and the Sphingolipid Rheostat. Front Immunol. 2017;8:597. doi:10.3389/fimmu.2017.00597Jernigan, P.L.; Makley, A.T.; Hoehn, R.S.; Edwards, M.J.; Pritts, T.A. The role of sphingolipids in endothelial barrier function. Biol. Chem. 2015, 396, 681–691.
  17. Knipe RS, Spinney JJ, Abe EA, et al. Endothelial-Specific Loss of Sphingosine-1-Phosphate Receptor 1 Increases Vascular Permeability and Exacerbates Bleomycin-induced Pulmonary Fibrosis. Am J Respir Cell Mol Biol. 2022;66(1):38-52. doi:10.1165/rcmb.2020-0408OCKuperberg, S.J.; Wadgaonkar, R. Sepsis-Associated Encephalopathy: The Blood-Brain Barrier and the Sphingolipid Rheostat. Front. Immunol. 2017, 8, 597.
  18. Knipe RS, Spinney JJ, Abe E, et al. Loss of endothelial S1PR1 exacerbates bleomycin-induced pulmonary fibrosis through intra-alveolar coagulation and immune cell infiltration. Am J Respir Crit Care Med. 2020;201(1). https://www.embase.com/search/results?subaction=viewrecord&id=L632376616&from=exportKnipe, R.S.; Spinney, J.J.; Abe, E.A.; Probst, C.K.; Franklin, A.; Logue, A.; Giacona, F.; Drummond, M.; Griffith, J.; Brazee, P.L.; et al. Endothelial-Specific Loss of Sphingosine-1-Phosphate Receptor 1 Increases Vascular Permeability and Exacerbates Bleomycin-induced Pulmonary Fibrosis. Am. J. Respir. Cell Mol. Biol. 2022, 66, 38–52.
  19. Wadgaonkar R, Patel V, Grinkina N, et al. Differential regulation of sphingosine kinases 1 and 2 in lung injury. Am J Physiol Lung Cell Mol Physiol. 2009;296(4):L603-613. doi:10.1152/ajplung.90357.2008Knipe, R.S.; Spinney, J.J.; Abe, E.; Probst, C.K.; Logue, A.; Griffith, J.; Black, K.E.; Montesi, S.B.; Shea, B.; Medoff, B.D. Loss of endothelial S1PR1 exacerbates bleomycin-induced pulmonary fibrosis through intra-alveolar coagulation and immune cell infiltration. Am. J. Respir. Crit. Care Med. 2020, 201, A7878.
  20. Villar J, Zhang H, Slutsky AS. Lung Repair and Regeneration in ARDS: Role of PECAM1 and Wnt Signaling. Chest. 2019;155(3):587-594. doi:10.1016/j.chest.2018.10.022Wadgaonkar, R.; Patel, V.; Grinkina, N.; Romano, C.; Liu, J.; Zhao, Y.; Sammani, S.; Garcia, J.G.N.; Natarajan, V. Differential regulation of sphingosine kinases 1 and 2 in lung injury. Am. J. Physiol. Lung Cell Mol. Physiol. 2009, 296, L603–L613.
  21. Probst CK, Montesi SB, Medoff BD, Shea BS, Knipe RS. Vascular permeability in the fibrotic lung. Eur Respir J. 2020;56(1):1900100. doi:10.1183/13993003.00100-2019Hay, J.; Shahzeidi, S.; Laurent, G. Mechanisms of bleomycin-induced lung damage. Arch. Toxicol. 1991, 65, 81–94.
  22. Engelbrecht E, Kooistra T, Knipe RS. The Vasculature in Pulmonary Fibrosis. Curr Tissue Microenviron Rep. 2022;3(4):83-97. doi:10.1007/s43152-022-00040-9Probst, C.K.; Montesi, S.B.; Medoff, B.D.; Shea, B.S.; Knipe, R.S. Vascular permeability in the fibrotic lung. Eur. Respir. J. 2020, 56, 1900100.
  23. Mehta D, Malik AB. Signaling mechanisms regulating endothelial permeability. Physiol Rev. 2006;86(1):279-367. doi:10.1152/physrev.00012.2005Villar, J.; Zhang, H.; Slutsky, A.S. Lung Repair and Regeneration in ARDS: Role of PECAM1 and Wnt Signaling. Chest 2019, 155, 587–594.
  24. Campbell HK, Maiers JL, DeMali KA. Interplay between tight junctions & adherens junctions. Exp Cell Res. 2017;358(1):39-44. doi:10.1016/j.yexcr.2017.03.061Engelbrecht, E.; Kooistra, T.; Knipe, R.S. The Vasculature in Pulmonary Fibrosis. Curr. Tissue Microenviron. Rep. 2022, 3, 83–97.
  25. Wettschureck N, Strilic B, Offermanns S. Passing the Vascular Barrier: Endothelial Signaling Processes Controlling Extravasation. Physiol Rev. 2019;99(3):1467-1525. doi:10.1152/physrev.00037.2018Komarova, Y.; Malik, A.B. Regulation of endothelial permeability via paracellular and transcellular transport pathways. Annu. Rev. Physiol. 2010, 72, 463–493.
  26. Oldenburg J, de Rooij J. Mechanical control of the endothelial barrier. Cell Tissue Res. 2014;355(3):545-555. doi:10.1007/s00441-013-1792-6Pober, J.S.; Sessa, W.C. Evolving functions of endothelial cells in inflammation. Nat. Rev. Immunol. 2007, 7, 803–815.
  27. Katoh K, Kano Y, Noda Y. Rho-associated kinase-dependent contraction of stress fibres and the organization of focal adhesions. J R Soc Interface. 2011;8(56):305-311. doi:10.1098/rsif.2010.0419Mehta, D.; Malik, A.B. Signaling mechanisms regulating endothelial permeability. Physiol. Rev. 2006, 86, 279–367.
  28. Wojciak-Stothard B, Ridley AJ. Rho GTPases and the regulation of endothelial permeability. Vascul Pharmacol. 2002;39(4-5):187-199. doi:10.1016/s1537-1891(03)00008-9Campbell, H.K.; Maiers, J.L.; DeMali, K.A. Interplay between tight junctions & adherens junctions. Exp. Cell. Res. 2017, 358, 39–44.
  29. Del Gaudio I, Camerer E. Distinct GEFs Couple S1PR1 to Rac for Endothelial Barrier Enhancement and Lymphocyte Trafficking. Arterioscler Thromb Vasc Biol. 2022;42(7):903-905. doi:10.1161/ATVBAHA.122.317794De Caterina, R.; Libby, P.; Peng, H.B.; Thannickal, V.J.; Rajavashisth, T.B.; Gimbrone, M.A.; Shin, W.S.; Liao, J.K. Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. J. Clin. Investig. 1995, 96, 60–68.
  30. Wadgaonkar R, Geraghty P, Kabir I, Foronjy R. Role of sphingomyelin synthase regulated micro domain signaling in cigarette smoke induced inflammation. Am J Respir Crit Care Med. 2017;195((Wadgaonkar R.; Geraghty P.; Kabir I.; Foronjy R.) SUNY Downstate Medical Center, Brooklyn, NY, United States). doi:10.1164/ajrccmconference.2017.C74Claesson-Welsh, L. Vascular permeability—The essentials. Ups. J. Med. Sci. 2015, 120, 135–143.
  31. Gowda S, Yeang C, Wadgaonkar S, et al. Sphingomyelin synthase 2 (SMS2) deficiency attenuates LPS-induced lung injury. Am J Physiol Lung Cell Mol Physiol. 2011;300(3):L430-440. doi:10.1152/ajplung.00208.2010Nagy, J.A.; Benjamin, L.; Zeng, H.; Dvorak, A.M.; Dvorak, H.F. Vascular permeability, vascular hyperpermeability and angiogenesis. Angiogenesis 2008, 11, 109–119.
  32. Wattenberg BW, Pitson SM, Raben DM. The sphingosine and diacylglycerol kinase superfamily of signaling kinases: localization as a key to signaling function. J Lipid Res. 2006;47(6):1128-1139. doi:10.1194/jlr.R600003-JLR200Wettschureck, N.; Strilic, B.; Offermanns, S. Passing the Vascular Barrier: Endothelial Signaling Processes Controlling Extravasation. Physiol. Rev. 2019, 99, 1467–1525.
  33. Siow DL, Anderson CD, Berdyshev EV, et al. Sphingosine kinase localization in the control of sphingolipid metabolism. Adv Enzyme Regul. 2011;51(1):229-244. doi:10.1016/j.advenzreg.2010.09.004Jambusaria, A.; Hong, Z.; Zhang, L.; Srivastava, S.; Jana, A.; Toth, P.T.; Dai, Y.; Malik, A.B.; Rehman, J. Endothelial heterogeneity across distinct vascular beds during homeostasis and inflammation. eLife 2020, 9, e51413.
  34. Bravo GÁ, Cedeño RR, Casadevall MP, Ramió-Torrentà L. Sphingosine-1-Phosphate (S1P) and S1P Signaling Pathway Modulators, from Current Insights to Future Perspectives. Cells. 2022;11(13):2058. doi:10.3390/cells11132058Shimoda, L.A.; Semenza, G.L. HIF and the lung: Role of hypoxia-inducible factors in pulmonary development and disease. Am. J. Respir. Crit. Care Med. 2011, 183, 152–156.
  35. Sanchez T, Skoura A, Wu MT, Casserly B, Harrington EO, Hla T. Induction of vascular permeability by the sphingosine-1-phosphate receptor-2 (S1P2R) and its downstream effectors ROCK and PTEN. Arterioscler Thromb Vasc Biol. 2007;27(6):1312-1318. doi:10.1161/ATVBAHA.107.143735Laddha, A.P.; Kulkarni, Y.A. VEGF and FGF-2: Promising targets for the treatment of respiratory disorders. Respir. Med. 2019, 156, 33–46.
  36. Sanchez T, Hla T. Structural and functional characteristics of S1P receptors. J Cell Biochem. 2004;92(5):913-922. doi:10.1002/jcb.20127Ramakrishnan, S.; Anand, V.; Roy, S. Vascular endothelial growth factor signaling in hypoxia and inflammation. J. Neuroimmune Pharmacol. 2014, 9, 142–160.
  37. Forrest M, Sun SY, Hajdu R, et al. Immune cell regulation and cardiovascular effects of sphingosine 1-phosphate receptor agonists in rodents are mediated via distinct receptor subtypes. J Pharmacol Exp Ther. 2004;309(2):758-768. doi:10.1124/jpet.103.062828Broermann, A.; Winderlich, M.; Block, H.; Frye, M.; Rossaint, J.; Zarbock, A.; Cagna, G.; Linnepe, R.; Schulte, D.; Nottebaum, A.F.; et al. Dissociation of VE-PTP from VE-cadherin is required for leukocyte extravasation and for VEGF-induced vascular permeability in vivo. J. Exp. Med. 2011, 208, 2393–2401.
  38. Jin F, Hagemann N, Sun L, et al. High-density lipoprotein (HDL) promotes angiogenesis via S1P3-dependent VEGFR2 activation. Angiogenesis. 2018;21(2):381-394. doi:10.1007/s10456-018-9603-zNottebaum, A.F.; Cagna, G.; Winderlich, M.; Gamp, A.C.; Linnepe, R.; Polaschegg, C.; Filippova, K.; Lyck, R.; Engelhardt, B.; Kamenyeva, O.; et al. VE-PTP maintains the endothelial barrier via plakoglobin and becomes dissociated from VE-cadherin by leukocytes and by VEGF. J. Exp. Med. 2008, 205, 2929–2945.
  39. Gräler MH, Grosse R, Kusch A, Kremmer E, Gudermann T, Lipp M. The sphingosine 1-phosphate receptor S1P4 regulates cell shape and motility via coupling to Gi and G12/13. J Cell Biochem. 2003;89(3):507-519. doi:10.1002/jcb.10537Oldenburg, J.; de Rooij, J. Mechanical control of the endothelial barrier. Cell Tissue Res. 2014, 355, 545–555.
  40. Niedernberg A, Scherer CR, Busch AE, Kostenis E. Comparative analysis of human and rat S1P(5) (edg8): differential expression profiles and sensitivities to antagonists. Biochem Pharmacol. 2002;64(8):1243-1250. doi:10.1016/s0006-2952(02)01289-3Nagatoya, K.; Moriyama, T.; Kawada, N.; Takeji, M.; Oseto, S.; Murozono, T.; Ando, A.; Imai, E.; Hori, M. Y-27632 prevents tubulointerstitial fibrosis in mouse kidneys with unilateral ureteral obstruction. Kidney Int. 2002, 61, 1684–1695.
  41. Garcia JG, Liu F, Verin AD, et al. Sphingosine 1-phosphate promotes endothelial cell barrier integrity by Edg-dependent cytoskeletal rearrangement. J Clin Invest. 2001;108(5):689-701. doi:10.1172/JCI12450Knipe, R.S.; Probst, C.K.; Lagares, D.; Franklin, A.; Spinney, J.J.; Brazee, P.L.; Grasberger, P.; Zhang, L.; Black, K.E.; Sakai, N.; et al. The Rho Kinase Isoforms ROCK1 and ROCK2 Each Contribute to the Development of Experimental Pulmonary Fibrosis. Am. J. Respir. Cell Mol. Biol. 2018, 58, 471–481.
  42. Berdyshev EV, Gorshkova I, Usatyuk P, et al. Intracellular S1P generation is essential for S1P-induced motility of human lung endothelial cells: role of sphingosine kinase 1 and S1P lyase. PloS One. 2011;6(1):e16571. doi:10.1371/journal.pone.0016571Kitamura, K.; Tada, S.; Nakamoto, N.; Toda, K.; Horikawa, H.; Kurita, S.; Tsunematsu, S.; Kumagai, N.; Ishii, H.; Saito, H.; et al. Rho/Rho kinase is a key enzyme system involved in the angiotensin II signaling pathway of liver fibrosis and steatosis. J. Gastroenterol. Hepatol. 2007, 22, 2022–2033.
  43. Adyshev DM, Moldobaeva NK, Elangovan VR, Garcia JGN, Dudek SM. Differential involvement of ezrin/radixin/moesin proteins in sphingosine 1-phosphate-induced human pulmonary endothelial cell barrier enhancement. Cell Signal. 2011;23(12):2086-2096. doi:10.1016/j.cellsig.2011.08.003Katoh, K.; Kano, Y.; Noda, Y. Rho-associated kinase-dependent contraction of stress fibres and the organization of focal adhesions. J. R. Soc. Interface 2011, 8, 305–311.
  44. Donati C, Bruni P. Sphingosine 1-phosphate regulates cytoskeleton dynamics: implications in its biological response. Biochim Biophys Acta. 2006;1758(12):2037-2048. doi:10.1016/j.bbamem.2006.06.015Wojciak-Stothard, B.; Ridley, A.J. Rho GTPases and the regulation of endothelial permeability. Vascul. Pharmacol. 2002, 39, 187–199.
  45. Sun X, Shikata Y, Wang L, et al. Enhanced interaction between focal adhesion and adherens junction proteins: involvement in sphingosine 1-phosphate-induced endothelial barrier enhancement. Microvasc Res. 2009;77(3):304-313. doi:10.1016/j.mvr.2008.12.004Mong, P.Y.; Wang, Q. Activation of Rho kinase isoforms in lung endothelial cells during inflammation. J. Immunol. 2009, 182, 2385–2394.
  46. Hla T, Brinkmann V. Sphingosine 1-phosphate (S1P): Physiology and the effects of S1P receptor modulation. Neurology. 2011;76(8 Suppl 3):S3-8. doi:10.1212/WNL.0b013e31820d5ec1Abbès, M.; Sabatier, P. . Ann. Chir. Plast. 1970, 15, 205–213.
  47. Bazzoni G, Dejana E. Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis. Physiol Rev. 2004;84(3):869-901. doi:10.1152/physrev.00035.2003Del Gaudio, I.; Camerer, E. Distinct GEFs Couple S1PR1 to Rac for Endothelial Barrier Enhancement and Lymphocyte Trafficking. Arterioscler Thromb. Vasc. Biol. 2022, 42, 903–905.
  48. Peng X, Hassoun PM, Sammani S, et al. Protective effects of sphingosine 1-phosphate in murine endotoxin-induced inflammatory lung injury. Am J Respir Crit Care Med. 2004;169(11):1245-1251. doi:10.1164/rccm.200309-1258OCWadgaonkar, R.; Geraghty, P.; Kabir, I.; Foronjy, R. Role of sphingomyelin synthase regulated micro domain signaling in cigarette smoke induced inflammation. Am. J. Respir. Crit. Care Med. 2017, 195, A6339.
  49. McVerry BJ, Peng X, Hassoun PM, Sammani S, Simon BA, Garcia JGN. Sphingosine 1-phosphate reduces vascular leak in murine and canine models of acute lung injury. Am J Respir Crit Care Med. 2004;170(9):987-993. doi:10.1164/rccm.200405-684OCGowda, S.; Yeang, C.; Wadgaonkar, S.; Anjum, F.; Grinkina, N.; Cutaia, M.; Jiang, X.-C.; Wadgaonkar, R. Sphingomyelin synthase 2 (SMS2) deficiency attenuates LPS-induced lung injury. Am. J. Physiol. Lung Cell Mol. Physiol. 2011, 300, L430–L440.
  50. Knipe RS, Spinney JJ, Abe E, et al. The pulmonary endothelium plays a critical role in the fibrotic response to lung injury through S1PR1 and rock mediated cytoskeletal rearrangements. Am J Respir Crit Care Med. 2019;199(9). https://www.embase.com/search/results?subaction=viewrecord&id=L630348969&from=exportWattenberg, B.W.; Pitson, S.M.; Raben, D.M. The sphingosine and diacylglycerol kinase superfamily of signaling kinases: Localization as a key to signaling function. J. Lipid Res. 2006, 47, 1128–1139.
  51. Knipe RS, Probst CK, Lagares D, et al. The Rho Kinase Isoforms ROCK1 and ROCK2 Each Contribute to the Development of Experimental Pulmonary Fibrosis. Am J Respir Cell Mol Biol. 2018;58(4):471-481. doi:10.1165/rcmb.2017-0075OCSiow, D.L.; Anderson, C.D.; Berdyshev, E.V.; Skobeleva, A.; Natarajan, V.; Pitson, S.M.; Wattenberg, B.W. Sphingosine kinase localization in the control of sphingolipid metabolism. Adv. Enzyme Regul. 2011, 51, 229–244.
  52. Shea BS, Probst CK, Brazee PL, et al. Uncoupling of the profibrotic and hemostatic effects of thrombin in lung fibrosis. JCI Insight. 2017;2(9):e86608, 86608. doi:10.1172/jci.insight.86608Bravo, G.A.; Cedeno, R.R.; Casadevall, M.P.; Ramio-Torrenta, L. Sphingosine-1-Phosphate (S1P) and S1P Signaling Pathway Modulators, from Current Insights to Future Perspectives. Cells 2022, 11, 2058.
  53. Milara J, Navarro R, Juan G, et al. Sphingosine-1-phosphate is increased in patients with idiopathic pulmonary fibrosis and mediates epithelial to mesenchymal transition. Thorax. 2012;67(2):147-156. doi:10.1136/thoraxjnl-2011-200026Sanchez, T.; Skoura, A.; Wu, M.T.; Casserly, B.; Harrington, E.O.; Hla, T. Induction of vascular permeability by the sphingosine-1-phosphate receptor-2 (S1P2R) and its downstream effectors ROCK and PTEN. Arterioscler Thromb. Vasc. Biol. 2007, 27, 1312–1318.
  54. Brinkmann V. FTY720 (fingolimod) in Multiple Sclerosis: therapeutic effects in the immune and the central nervous system. Br J Pharmacol. 2009;158(5):1173-1182. doi:10.1111/j.1476-5381.2009.00451.xSanchez, T.; Hla, T. Structural and functional characteristics of S1P receptors. J. Cell. Biochem. 2004, 92, 913–922.
  55. Garnier O, Vilgrain I. Dialogue between VE-Cadherin and Sphingosine 1 Phosphate Receptor1 (S1PR1) for Protecting Endothelial Functions. Int J Mol Sci. 2023;24(4):4018. doi:10.3390/ijms24044018Forrest, M.; Sun, S.Y.; Hajdu, R.; Bergstrom, J.; Card, D.; Doherty, G.; Hale, J.; Keohane, C.; Meyers, C.; Milligan, J.; et al. Immune cell regulation and cardiovascular effects of sphingosine 1-phosphate receptor agonists in rodents are mediated via distinct receptor subtypes. J. Pharmacol. Exp. Ther. 2004, 309, 758–768.
  56. Leonard A, Grose V, Paton AW, et al. Selective Inactivation of Intracellular BiP/GRP78 Attenuates Endothelial Inflammation and Permeability in Acute Lung Injury. Sci Rep. 2019;9(1):2096. doi:10.1038/s41598-018-38312-wJin, F.; Hagemann, N.; Sun, L.; Wu, J.; Doeppner, T.R.; Dai, Y.; Hermann, D.M. High-density lipoprotein (HDL) promotes angiogenesis via S1P3-dependent VEGFR2 activation. Angiogenesis 2018, 21, 381–394.
  57. Zhao J, Okamoto Y, Asano Y, et al. Sphingosine-1-phosphate receptor-2 facilitates pulmonary fibrosis through potentiating IL-13 pathway in macrophages. PloS One. 2018;13(5):e0197604. doi:10.1371/journal.pone.0197604Gräler, M.H.; Grosse, R.; Kusch, A.; Kremmer, E.; Gudermann, T.; Lipp, M. The sphingosine 1-phosphate receptor S1P4 regulates cell shape and motility via coupling to Gi and G12/13. J. Cell. Biochem. 2003, 89, 507–519.
  58. Natarajan V, Dudek SM, Jacobson JR, et al. Sphingosine-1-phosphate, FTY720, and sphingosine-1-phosphate receptors in the pathobiology of acute lung injury. Am J Respir Cell Mol Biol. 2013;49(1):6-17. doi:10.1165/rcmb.2012-0411TRNiedernberg, A.; Scherer, C.R.; Busch, A.E.; Kostenis, E. Comparative analysis of human and rat S1P(5) (edg8): Differential expression profiles and sensitivities to antagonists. Biochem. Pharmacol. 2002, 64, 1243–1250.
  59. Sammani S, Moreno-Vinasco L, Mirzapoiazova T, et al. Differential effects of sphingosine 1-phosphate receptors on airway and vascular barrier function in the murine lung. Am J Respir Cell Mol Biol. 2010;43(4):394-402. doi:10.1165/rcmb.2009-0223OCGarcia, J.G.; Liu, F.; Verin, A.D.; Birukova, A.; Dechert, M.A.; Gerthoffer, W.T.; Bamberg, J.R.; English, D. Sphingosine 1-phosphate promotes endothelial cell barrier integrity by Edg-dependent cytoskeletal rearrangement. J. Clin. Investig. 2001, 108, 689–701.
  60. Wang Y, Gao TT, Xu DF, et al. Upregulation of sphingosine kinase 1 contributes to ventilator-associated lung injury in a two-hit model. Int J Mol Med. 2019;44(6):2077-2090. doi:10.3892/ijmm.2019.4379Berdyshev, E.V.; Gorshkova, I.; Usatyuk, P.; Kalari, S.; Zhao, Y.; Pyne, N.J.; Pyne, S.; Sabbadini, R.A.; Garcia, J.G.N.; Natarajan, V. Intracellular S1P generation is essential for S1P-induced motility of human lung endothelial cells: Role of sphingosine kinase 1 and S1P lyase. PLoS ONE 2011, 6, e16571.
  61. Adyshev, D.M.; Moldobaeva, N.K.; Elangovan, V.R.; Garcia, J.G.N.; Dudek, S.M. Differential involvement of ezrin/radixin/moesin proteins in sphingosine 1-phosphate-induced human pulmonary endothelial cell barrier enhancement. Cell Signal. 2011, 23, 2086–2096.
  62. Donati, C.; Bruni, P. Sphingosine 1-phosphate regulates cytoskeleton dynamics: Implications in its biological response. Biochim. Biophys. Acta 2006, 1758, 2037–2048.
  63. Sun, X.; Shikata, Y.; Wang, L.; Ohmori, K.; Watanabe, N.; Wada, J.; Shikata, K.; Birukov, K.G.; Makino, H.; Jacobson, J.R.; et al. Enhanced interaction between focal adhesion and adherens junction proteins: Involvement in sphingosine 1-phosphate-induced endothelial barrier enhancement. Microvasc. Res. 2009, 77, 304–313.
  64. Hla, T.; Brinkmann, V. Sphingosine 1-phosphate (S1P): Physiology and the effects of S1P receptor modulation. Neurology 2011, 76, S3–S8.
  65. Bazzoni, G.; Dejana, E. Endothelial cell-to-cell junctions: Molecular organization and role in vascular homeostasis. Physiol. Rev. 2004, 84, 869–901.
  66. Natarajan, V.; Dudek, S.M.; Jacobson, J.R.; Moreno-Vinasco, L.; Huang, L.S.; Abassi, T.; Mathew, B.; Zhao, Y.; Wang, L.; Bittman, R.; et al. Sphingosine-1-phosphate, FTY720, and sphingosine-1-phosphate receptors in the pathobiology of acute lung injury. Am. J. Respir. Cell Mol. Biol. 2013, 49, 6–17.
  67. Peng, X.; Hassoun, P.M.; Sammani, S.; McVerry, B.J.; Burne, M.J.; Rabb, H.; Pearse, D.; Tuder, R.M.; Garcia, J.G.N. Protective effects of sphingosine 1-phosphate in murine endotoxin-induced inflammatory lung injury. Am. J. Respir. Crit. Care Med. 2004, 169, 1245–1251.
  68. McVerry, B.J.; Peng, X.; Hassoun, P.M.; Sammani, S.; Simon, B.A.; Garcia, J.G.N. Sphingosine 1-phosphate reduces vascular leak in murine and canine models of acute lung injury. Am. J. Respir. Crit. Care Med. 2004, 170, 987–993.
  69. Knipe, R.S.; Spinney, J.J.; Abe, E.; Probst, C.K.; Franklin, A.; Griffith, J.W.; Liao, J.K.; McCarthy, J.R.; Shea, B.S.; Medoff, B.D. The pulmonary endothelium plays a critical role in the fibrotic response to lung injury through S1PR1 and rock mediated cytoskeletal rearrangements. Am. J. Respir. Crit. Care Med. 2019, 199, A4020.
  70. Shea, B.S.; Probst, C.K.; Brazee, P.L.; Rotile, N.J.; Blasi, F.; Weinreb, P.H.; Black, K.E.; Sosnovik, D.E.; Van Cott, E.M.; Violette, S.M.; et al. Uncoupling of the profibrotic and hemostatic effects of thrombin in lung fibrosis. JCI Insight 2017, 2, e86608.
  71. Milara, J.; Navarro, R.; Juan, G.; Peiro, T.; Serrano, A.; Ramon, M.; Morcillo, E.; Cortijo, J. Sphingosine-1-phosphate is increased in patients with idiopathic pulmonary fibrosis and mediates epithelial to mesenchymal transition. Thorax 2012, 67, 147–156.
  72. Brinkmann, V. FTY720 (fingolimod) in Multiple Sclerosis: Therapeutic effects in the immune and the central nervous system. Br. J. Pharmacol. 2009, 158, 1173–1182.
  73. Garnier, O.; Vilgrain, I. Dialogue between VE-Cadherin and Sphingosine 1 Phosphate Receptor1 (S1PR1) for Protecting Endothelial Functions. Int. J. Mol. Sci. 2023, 24, 4018.
  74. Leonard, A.; Grose, V.; Paton, A.W.; Paton, J.C.; Yule, D.I.; Rahman, A.; Fazal, F. Selective Inactivation of Intracellular BiP/GRP78 Attenuates Endothelial Inflammation and Permeability in Acute Lung Injury. Sci. Rep. 2019, 9, 2096.
  75. Shea, B.S.; Brooks, S.F.; Fontaine, B.A.; Chun, J.; Luster, A.D.; Tager, A.M. Prolonged exposure to sphingosine 1-phosphate receptor-1 agonists exacerbates vascular leak, fibrosis, and mortality after lung injury. Am. J. Respir. Cell Mol. Biol. 2010, 43, 662–673.
  76. Zhao, J.; Okamoto, Y.; Asano, Y.; Ishimaru, K.; Aki, S.; Yoshioka, K.; Takuwa, N.; Wada, T.; Inagaki, Y.; Takahashi, C.; et al. Sphingosine-1-phosphate receptor-2 facilitates pulmonary fibrosis through potentiating IL-13 pathway in macrophages. PLoS ONE 2018, 13, e0197604.
  77. Sammani, S.; Moreno-Vinasco, L.; Mirzapoiazova, T.; Singleton, P.A.; Chiang, E.T.; Evenoski, C.L.; Wang, T.; Mathew, B.; Husain, A.; Moitra, J.; et al. Differential effects of sphingosine 1-phosphate receptors on airway and vascular barrier function in the murine lung. Am. J. Respir. Cell Mol. Biol. 2010, 43, 394–402.
  78. Wang, Y.; Gao, T.-T.; Xu, D.-F.; Zhu, X.-Y.; Dong, W.-W.; Lv, Z.; Liu, Y.-J.; Jiang, L. Upregulation of sphingosine kinase 1 contributes to ventilator-associated lung injury in a two-hit model. Int. J. Mol. Med. 2019, 44, 2077–2090.
  79. Calabresi, P.A.; Radue, E.-W.; Goodin, D.; Jeffery, D.; Rammohan, K.W.; Reder, A.T.; Vollmer, T.; Agius, M.A.; Kappos, L.; Stites, T.; et al. Safety and efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (FREEDOMS II): A double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Neurol. 2014, 13, 545–556.
  80. Cohen, J.A.; Khatri, B.; Barkhof, F.; Comi, G.; Hartung, H.-P.; Montalban, X.; Pelletier, J.; Stites, T.; Ritter, S.; von Rosenstiel, P.; et al. Long-term (up to 4.5 years) treatment with fingolimod in multiple sclerosis: Results from the extension of the randomised TRANSFORMS study. J. Neurol. Neurosurg. Psychiatry 2016, 87, 468–475.
  81. Khatri, B.; Barkhof, F.; Comi, G.; Hartung, H.-P.; Kappos, L.; Montalban, X.; Pelletier, J.; Stites, T.; Wu, S.; Holdbrook, F.; et al. Comparison of fingolimod with interferon beta-1a in relapsing-remitting multiple sclerosis: A randomised extension of the TRANSFORMS study. Lancet Neurol. 2011, 10, 520–529.
  82. Lublin, F.; Miller, D.H.; Freedman, M.S.; Cree, B.A.C.; Wolinsky, J.S.; Weiner, H.; Lubetzki, C.; Hartung, H.-P.; Montalban, X.; Uitdehaag, B.M.J.; et al. Oral fingolimod in primary progressive multiple sclerosis (INFORMS): A phase 3, randomised, double-blind, placebo-controlled trial. Lancet 2016, 387, 1075–1084.
  83. Kong, Y.; Wang, H.; Wang, S.; Tang, N. FTY720, a sphingosine-1 phosphate receptor modulator, improves liver fibrosis in a mouse model by impairing the motility of bone marrow-derived mesenchymal stem cells. Inflammation 2014, 37, 1326–1336.
  84. Ni, H.; Chen, J.; Pan, M.; Zhang, M.; Zhang, J.; Chen, P.; Liu, B. FTY720 prevents progression of renal fibrosis by inhibiting renal microvasculature endothelial dysfunction in a rat model of chronic kidney disease. J. Mol. Histol. 2013, 44, 693–703.
  85. Qian, J.; Ye, Y.; Lv, L.; Zhu, C.; Ye, S. FTY720 attenuates paraquat-induced lung injury in mice. Int. Immunopharmacol. 2014, 21, 426–431.
  86. Liu, W.D.; Gao, G.; Liu, H.Y.; Yan, G.H.; Li, L.C.; Zhang, J.Y.; Cui, H. Effects of fty-720 on pulmonary fibrosis in mice via tgf-pl/p38 mapk/nf-kb signaling pathway. Chin. Pharmacol. Bull. 2020, 36, 250–256.
  87. Muller, H.C.; Hocke, A.C.; Hellwig, K.; Gutbier, B.; Peters, H.; Schonrock, S.M.; Tschernig, T.; Schmiedl, A.; Hippenstiel, S.; N’Guessan, P.D.; et al. The Sphingosine-1 Phosphate receptor agonist FTY720 dose dependently affected endothelial integrity in vitro and aggravated ventilator-induced lung injury in mice. Pulm. Pharmacol. Ther. 2011, 24, 377–385.
  88. Gendron, D.R.; Lemay, A.-M.; Lecours, P.B.; Perreault-Vallières, V.; Huppé, C.-A.; Bossé, Y.; Blanchet, M.-R.; Dion, G.; Marsolais, D. FTY720 promotes pulmonary fibrosis when administered during the remodelling phase following a bleomycin-induced lung injury. Pulm. Pharmacol. Ther. 2017, 44, 50–56.
  89. Sobel, K.; Menyhart, K.; Killer, N.; Renault, B.; Bauer, Y.; Studer, R.; Steiner, B.; Bolli, M.H.; Nayler, O.; Gatfield, J. Sphingosine 1-phosphate (S1P) receptor agonists mediate pro-fibrotic responses in normal human lung fibroblasts via S1P2 and S1P3 receptors and Smad-independent signaling. J. Biol. Chem. 2013, 288, 14839–14851.
  90. Keller, C.D.; Rivera Gil, P.; Tolle, M.; van der Giet, M.; Chun, J.; Radeke, H.H.; Schafer-Korting, M.; Kleuser, B. Immunomodulator FTY720 induces myofibroblast differentiation via the lysophospholipid receptor S1P3 and Smad3 signaling. Am. J. Pathol. 2007, 170, 281–292.
  91. Clemons, B.; Bain, G.; Lai, A.; Santini, A.M.; Goulet, L.; Boyett, M.; Roberts, E.; Rosen, H.; Opiteck, G.J.; Scott, F.L.; et al. Favourable S1P1R/5R selectivity profile of ozanimod confers safety benefit relating to S1P3R-mediated pro-fibrotic changes in fibroblasts. Mult. Scler. J. 2018, 24, 39.
  92. Pérez-Jeldres, T.; Alvarez-Lobos, M.; Rivera-Nieves, J. Targeting Sphingosine-1-Phosphate Signaling in Immune-Mediated Diseases: Beyond Multiple Sclerosis. Drugs 2021, 81, 985–1002.
  93. Karnati, S.; Seimetz, M.; Kleefeldt, F.; Sonawane, A.; Madhusudhan, T.; Bachhuka, A.; Kosanovic, D.; Weissmann, N.; Krüger, K.; Ergün, S. Chronic Obstructive Pulmonary Disease and the Cardiovascular System: Vascular Repair and Regeneration as a Therapeutic Target. Front. Cardiovasc. Med. 2021, 8, 649512.
  94. Ebina, M.; Shimizukawa, M.; Shibata, N.; Kimura, Y.; Suzuki, T.; Endo, M.; Sasano, H.; Kondo, T.; Nukiwa, T. Heterogeneous increase in CD34-positive alveolar capillaries in idiopathic pulmonary fibrosis. Am. J. Respir. Crit. Care Med. 2004, 169, 1203–1208.
  95. Simler, N.R.; Brenchley, P.E.; Horrocks, A.W.; Greaves, S.M.; Hasleton, P.S.; Egan, J.J. Angiogenic cytokines in patients with idiopathic interstitial pneumonia. Thorax 2004, 59, 581–585.
  96. Cosgrove, G.P.; Brown, K.K.; Schiemann, W.P.; Serls, A.E.; Parr, J.E.; Geraci, M.W.; Schwarz, M.I.; Cool, C.D.; Worthen, G.S. Pigment epithelium-derived factor in idiopathic pulmonary fibrosis: A role in aberrant angiogenesis. Am. J. Respir. Crit. Care Med. 2004, 170, 242–251.
  97. Liu, X.; Qin, X.; Qin, H.; Jia, C.; Yuan, Y.; Sun, T.; Chen, B.; Chen, C.; Zhang, H. Characterization of the heterogeneity of endothelial cells in bleomycin-induced lung fibrosis using single-cell RNA sequencing. Angiogenesis 2021, 24, 809–821.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)
ScholarVision Creations
Feedback