REFERENCES
2. Roehlen N, Crouchet E, Baumert TF. Liver fibrosis: mechanistic concepts and therapeutic perspectives. Cells 2020;9:875.
3. Ginès P, Krag A, Abraldes JG, Solà E, Fabrellas N, Kamath PS. Liver cirrhosis. Lancet 2021;398:1359-76.
4. Neshat SY, Quiroz VM, Wang Y, Tamayo S, Doloff JC. Liver disease: induction, progression, immunological mechanisms, and therapeutic interventions. Int J Mol Sci 2021;22:6777.
5. Loewith R, Riezman H, Winssinger N. Sphingolipids and membrane targets for therapeutics. Curr Opin Chem Biol 2019;50:19-28.
6. Calzada C, Vors C, Penhoat A, Cheillan D, Michalski MC. Role of circulating sphingolipids in lipid metabolism: why dietary lipids matter. Front Nutr 2022;9:1108098.
7. Rao R, Vaidyanathan N, Rengasamy M, Mammen Oommen A, Somaiya N, Jagannath MR. Sphingolipid metabolic pathway: an overview of major roles played in human diseases. J Lipids 2013;2013:178910.
8. Quinville BM, Deschenes NM, Ryckman AE, Walia JS. A comprehensive review: sphingolipid metabolism and implications of disruption in sphingolipid homeostasis. Int J Mol Sci 2021;22:5793.
9. Xiao S, Peng K, Li C, Long Y, Yu Q. The role of sphingosine-1-phosphate in autophagy and related disorders. Cell Death Discov 2023;9:380.
10. Nojima H, Shimizu H, Murakami T, Shuto K, Koda K. Critical roles of the sphingolipid metabolic pathway in liver regeneration, hepatocellular carcinoma progression and therapy. Cancers (Basel) 2024;16:850.
11. Zhu C, Huai Q, Zhang X, Dai H, Li X, Wang H. Insights into the roles and pathomechanisms of ceramide and sphigosine-1-phosphate in nonalcoholic fatty liver disease. Int J Biol Sci 2023;19:311-30.
12. Ishay Y, Nachman D, Khoury T, Ilan Y. The role of the sphingolipid pathway in liver fibrosis: an emerging new potential target for novel therapies. Am J Physiol Cell Physiol 2020;318:C1055-64.
13. Jackson KG, Way GW, Zhou H. Bile acids and sphingolipids in non-alcoholic fatty liver disease. Chin Med J (Engl) 2022;135:1163-71.
14. Luo N, Li J, Wei Y, Lu J, Dong R. Hepatic stellate cell: a double-edged sword in the liver. Physiol Res 2021;70:821-9.
15. Simon J, Ouro A, Ala-Ibanibo L, Presa N, Delgado TC, Martínez-Chantar ML. Sphingolipids in non-alcoholic fatty liver disease and hepatocellular carcinoma: ceramide turnover. Int J Mol Sci 2019;21:40.
16. Chang H, Meng HY, Liu SM, et al. Identification of key metabolic changes during liver fibrosis progression in rats using a urine and serum metabolomics approach. Sci Rep 2017;7:11433.
17. Holland WL, Summers SA. Sphingolipids, insulin resistance, and metabolic disease: new insights from in vivo manipulation of sphingolipid metabolism. Endocr Rev 2008;29:381-402.
18. Park KH, Ye ZW, Zhang J, et al. 3-ketodihydrosphingosine reductase mutation induces steatosis and hepatic injury in zebrafish. Sci Rep 2019;9:1138.
19. Mullen TD, Hannun YA, Obeid LM. Ceramide synthases at the centre of sphingolipid metabolism and biology. Biochem J 2012;441:789-802.
21. Bartke N, Hannun YA. Bioactive sphingolipids: metabolism and function. J Lipid Res 2009;50 Suppl:S91-6.
22. Reza S, Ugorski M, Suchański J. Glucosylceramide and galactosylceramide, small glycosphingolipids with significant impact on health and disease. Glycobiology 2021;31:1416-34.
23. Lee M, Lee SY, Bae YS. Functional roles of sphingolipids in immunity and their implication in disease. Exp Mol Med 2023;55:1110-30.
24. Yang F, Chen G. The nutritional functions of dietary sphingomyelin and its applications in food. Front Nutr 2022;9:1002574.
25. Jamjoum R, Majumder S, Issleny B, Stiban J. Mysterious sphingolipids: metabolic interrelationships at the center of pathophysiology. Front Physiol 2023;14:1229108.
26. Hla T. Physiological and pathological actions of sphingosine 1-phosphate. Semin Cell Dev Biol 2004;15:513-20.
27. Spiegel S, Milstien S. Sphingosine-1-phosphate: an enigmatic signalling lipid. Nat Rev Mol Cell Biol 2003;4:397-407.
28. Grassi S, Mauri L, Prioni S, et al. Sphingosine 1-phosphate receptors and metabolic enzymes as druggable targets for brain diseases. Front Pharmacol 2019;10:807.
29. Yu XD, Wang JW. Ceramide de novo synthesis in non-alcoholic fatty liver disease: pathogenic mechanisms and therapeutic perspectives. Biochem Pharmacol 2022;202:115157.
30. Thomas S, Samuel SV, Hoch A, Syphurs C, Diray-Arce J. The implication of sphingolipids in viral infections. Int J Mol Sci 2023;24:17303.
31. Bouscary A, Quessada C, René F, et al. Sphingolipids metabolism alteration in the central nervous system: amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. Semin Cell Dev Biol 2021;112:82-91.
32. Janneh AH, Ogretmen B. Targeting sphingolipid metabolism as a therapeutic strategy in cancer treatment. Cancers (Basel) 2022;14:2183.
33. Gomez-Larrauri A, Presa N, Dominguez-Herrera A, Ouro A, Trueba M, Gomez-Muñoz A. Role of bioactive sphingolipids in physiology and pathology. Essays Biochem 2020;64:579-89.
34. Aji G, Huang Y, Ng ML, et al. Regulation of hepatic insulin signaling and glucose homeostasis by sphingosine kinase 2. Proc Natl Acad Sci U S A 2020;117:24434-42.
35. Wigger D, Schumacher F, Schneider-Schaulies S, Kleuser B. Sphingosine 1-phosphate metabolism and insulin signaling. Cell Signal 2021;82:109959.
36. Piccoli M, Cirillo F, Ghiroldi A, et al. Sphingolipids and atherosclerosis: the dual role of ceramide and sphingosine-1-phosphate. Antioxidants (Basel) 2023;12:143.
37. Arosio B, Corbi G, Davinelli S, et al. Sex differences in cardiovascular diseases: a matter of estrogens, ceramides, and sphingosine 1-phosphate. Int J Mol Sci 2022;23:4009.
38. Peschel G, Weigand K, Grimm J, et al. Gender-specific differences in serum sphingomyelin species in patients with hepatitis c virus infection-sphingomyelin species are related to the model of end-stage liver disease (MELD) score in male patients. Int J Mol Sci 2023;24:8402.
39. Kisseleva T, Brenner D. Molecular and cellular mechanisms of liver fibrosis and its regression. Nat Rev Gastroenterol Hepatol 2021;18:151-66.
40. Heyens LJM, Busschots D, Koek GH, Robaeys G, Francque S. Liver fibrosis in non-alcoholic fatty liver disease: from liver biopsy to non-invasive biomarkers in diagnosis and treatment. Front Med (Lausanne) 2021;8:615978.
41. Kamm DR, McCommis KS. Hepatic stellate cells in physiology and pathology. J Physiol 2022;600:1825-37.
42. Garbuzenko DV. Pathophysiological mechanisms of hepatic stellate cells activation in liver fibrosis. World J Clin Cases 2022;10:3662-76.
43. Gandhi CR. Oxidative stress and hepatic stellate cells: a paradoxical relationship. Trends Cell Mol Biol 2012;7:1-10.
44. Khomich O, Ivanov AV, Bartosch B. Metabolic hallmarks of hepatic stellate cells in liver fibrosis. Cells 2019;9:24.
45. Wang Z, Du K, Jin N, Tang B, Zhang W. Macrophage in liver fibrosis: identities and mechanisms. Int Immunopharmacol 2023;120:110357.
46. Nguyen-Lefebvre AT, Horuzsko A. Kupffer cell metabolism and function. J Enzymol Metab 2015;1:101.
47. Qian J, Jiao Y, Wang G, Liu H, Cao X, Yang H. Mechanism of TGF-β1 inhibiting kupffer cell immune responses in cholestatic cirrhosis. Exp Ther Med 2020;20:1541-9.
48. Glaser SS, Gaudio E, Miller T, Alvaro D, Alpini G. Cholangiocyte proliferation and liver fibrosis. Expert Rev Mol Med 2009;11:e7.
50. Cai X, Tacke F, Guillot A, Liu H. Cholangiokines: undervalued modulators in the hepatic microenvironment. Front Immunol 2023;14:1192840.
51. Pham L, Kennedy L, Baiocchi L, et al. Mast cells in liver disease progression: an update on current studies and implications. Hepatology 2022;75:213-8.
52. Canbay A, Friedman S, Gores GJ. Apoptosis: the nexus of liver injury and fibrosis. Hepatology 2004;39:273-8.
53. Kim HY, Sakane S, Eguileor A, et al. The origin and fate of liver myofibroblasts. Cell Mol Gastroenterol Hepatol 2024;17:93-106.
54. Xu J, Kisseleva T. Bone marrow-derived fibrocytes contribute to liver fibrosis. Exp Biol Med (Maywood) 2015;240:691-700.
55. Lafoz E, Ruart M, Anton A, Oncins A, Hernández-Gea V. The endothelium as a driver of liver fibrosis and regeneration. Cells 2020;9:929.
56. Tang J, Yan Z, Feng Q, Yu L, Wang H. The roles of neutrophils in the pathogenesis of liver diseases. Front Immunol 2021;12:625472.
57. Rahman AH, Aloman C. Dendritic cells and liver fibrosis. Biochim Biophys Acta 2013;1832:998-1004.
59. Sun Y, Liu B, Xie J, et al. Aspirin attenuates liver fibrosis by suppressing TGF‑β1/Smad signaling. Mol Med Rep 2022;25:181.
60. Zhao M, Wang L, Wang M, et al. Targeting fibrosis, mechanisms and cilinical trials. Signal Transduct Target Ther 2022;7:206.
61. Ying HZ, Chen Q, Zhang WY, et al. PDGF signaling pathway in hepatic fibrosis pathogenesis and therapeutics (review). Mol Med Rep 2017;16:7879-89.
62. Liu J, Wang F, Luo F. The role of JAK/STAT pathway in fibrotic diseases: molecular and cellular mechanisms. Biomolecules 2023;13:119.
63. El-Ashmawy NE, Al-Ashmawy GM, Fakher HE, Khedr NF. The role of WNT/β-catenin signaling pathway and glutamine metabolism in the pathogenesis of CCl(4)-induced liver fibrosis: repositioning of niclosamide and concerns about lithium. Cytokine 2020;136:155250.
64. Duspara K, Bojanic K, Pejic JI, et al. Targeting the Wnt signaling pathway in liver fibrosis for drug options: an update. J Clin Transl Hepatol 2021;9:960-71.
65. Shen X, Peng Y, Li H. The injury-related activation of hedgehog signaling pathway modulates the repair-associated inflammation in liver fibrosis. Front Immunol 2017;8:1450.
66. Salgado Alvarez GA, Pinto Galvez SM, Garcia Mora U, et al. Higher cardiovascular risk scores and liver fibrosis risk estimated by biomarkers in patients with metabolic-dysfunction-associated fatty liver disease. World J Hepatol 2022;14:1633-42.
67. Sato M, Ikeda H, Uranbileg B, et al. Sphingosine kinase-1, S1P transporter spinster homolog 2 and S1P2 mRNA expressions are increased in liver with advanced fibrosis in human. Sci Rep 2016;6:32119.
68. Osawa Y, Kawai H, Nakashima K, et al. Sphingosine-1-phosphate promotes liver fibrosis in metabolic dysfunction-associated steatohepatitis. PLoS One 2024;19:e0303296.
69. Ding BS, Liu CH, Sun Y, et al. HDL activation of endothelial sphingosine-1-phosphate receptor-1 (S1P(1)) promotes regeneration and suppresses fibrosis in the liver. JCI Insight 2016;1:e87058.
70. Liu X, Yue S, Li C, Yang L, You H, Li L. Essential roles of sphingosine 1-phosphate receptor types 1 and 3 in human hepatic stellate cells motility and activation. J Cell Physiol 2011;226:2370-7.
71. Yang L, Chang N, Liu X, et al. Bone marrow-derived mesenchymal stem cells differentiate to hepatic myofibroblasts by transforming growth factor-β1 via sphingosine kinase/sphingosine 1-phosphate (S1P)/S1P receptor axis. Am J Pathol 2012;181:85-97.
72. Hou L, Yang L, Chang N, et al. Macrophage sphingosine 1-phosphate receptor 2 blockade attenuates liver inflammation and fibrogenesis triggered by NLRP3 inflammasome. Front Immunol 2020;11:1149.
73. King A, Houlihan DD, Kavanagh D, et al. Sphingosine-1-phosphate prevents egress of hematopoietic stem cells from liver to reduce fibrosis. Gastroenterology 2017;153:233-248.e16.
74. Nagahashi M, Takabe K, Liu R, et al. Conjugated bile acid-activated S1P receptor 2 is a key regulator of sphingosine kinase 2 and hepatic gene expression. Hepatology 2015;61:1216-26.
75. Xiao Y, Liu R, Li X, et al. Long noncoding RNA H19 contributes to cholangiocyte proliferation and cholestatic liver fibrosis in biliary atresia. Hepatology 2019;70:1658-73.
76. Islam D, Israr I, Taleb MAB, et al. A novel model to study mechanisms of cholestasis in human cholangiocytes reveals a role for the SIPR2 pathway. Hepatol Commun 2024:8.
77. Yang J, Tang X, Liang Z, Chen M, Sun L. Taurocholic acid promotes hepatic stellate cell activation via S1PR2/p38 MAPK/YAP signaling under cholestatic conditions. Clin Mol Hepatol 2023;29:465-81.
78. Ikeda H, Watanabe N, Ishii I, et al. Sphingosine 1-phosphate regulates regeneration and fibrosis after liver injury via sphingosine 1-phosphate receptor 2. J Lipid Res 2009;50:556-64.
79. Brunati AM, Tibaldi E, Carraro A, et al. Cross-talk between PDGF and S1P signalling elucidates the inhibitory effect and potential antifibrotic action of the immunomodulator FTY720 in activated HSC-cultures. Biochim Biophys Acta 2008;1783:347-59.
80. Kawai H, Osawa Y, Matsuda M, et al. Sphingosine-1-phosphate promotes tumor development and liver fibrosis in mouse model of congestive hepatopathy. Hepatology 2022;76:112-25.
81. Yang L, Yue S, Yang L, et al. Sphingosine kinase/sphingosine 1-phosphate (S1P)/S1P receptor axis is involved in liver fibrosis-associated angiogenesis. J Hepatol 2013;59:114-23.
82. Liao CY, Song MJ, Gao Y, Mauer AS, Revzin A, Malhi H. Hepatocyte-derived lipotoxic extracellular vesicle sphingosine 1-phosphate induces macrophage chemotaxis. Front Immunol 2018;9:2980.
83. Fadel F, Fayyaz S, Japtok L, Kleuser B. Involvement of sphingosine 1-phosphate in palmitate-induced non-alcoholic fatty liver disease. Cell Physiol Biochem 2016;40:1637-45.
84. Montefusco D, Jamil M, Maczis MA, et al. Sphingosine kinase 1 mediates sexual dimorphism in fibrosis in a mouse model of NASH. Mol Metab 2022;62:101523.
85. Liao Y, Zhou C, Duan Y, et al. Liver sinusoidal endothelial S1pr2 regulates experimental liver fibrosis through YAP/TGF-β signaling pathway. FASEB J 2023;37:e22905.
86. Nojima H, Freeman CM, Schuster RM, et al. Hepatocyte exosomes mediate liver repair and regeneration via sphingosine-1-phosphate. J Hepatol 2016;64:60-8.
87. Sugimoto M, Hamada T, Wakabayasi M, et al. Sphingomyelin synthase 2 loss suppresses steatosis but exacerbates fibrosis in the liver of mice fed with choline-deficient, L-amino acid-defined, high-fat diet. Biochem Biophys Res Commun 2020;533:1269-75.
88. Lee AY, Lee JW, Kim JE, et al. Dihydroceramide is a key metabolite that regulates autophagy and promotes fibrosis in hepatic steatosis model. Biochem Biophys Res Commun 2017;494:460-9.
89. Thiele M, Suvitaival T, Trošt K, et al. MicrobLiver Consortium; GALAXY Consortium. Sphingolipids are depleted in alcohol-related liver fibrosis. Gastroenterology 2023;164:1248-60.
90. Baweja S, Kumari A, Negi P, et al. Hepatopulmonary syndrome is associated with low sphingosine-1-phosphate levels and can be ameliorated by the functional agonist fingolimod. J Hepatol 2023;79:167-80.
91. McGinley MP, Cohen JA. Sphingosine 1-phosphate receptor modulators in multiple sclerosis and other conditions. Lancet 2021;398:1184-94.
92. Sandborn WJ, Vermeire S, Peyrin-Biroulet L, et al. Etrasimod as induction and maintenance therapy for ulcerative colitis (ELEVATE): two randomised, double-blind, placebo-controlled, phase 3 studies. Lancet 2023;401:1159-71.
93. Mauer AS, Hirsova P, Maiers JL, Shah VH, Malhi H. Inhibition of sphingosine 1-phosphate signaling ameliorates murine nonalcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol 2017;312:G300-13.
94. Wang Y, Aoki H, Yang J, et al. The role of sphingosine 1-phosphate receptor 2 in bile-acid-induced cholangiocyte proliferation and cholestasis-induced liver injury in mice. Hepatology 2017;65:2005-18.
95. Yang L, Han Z, Tian L, et al. Sphingosine 1-phosphate receptor 2 and 3 mediate bone marrow-derived monocyte/macrophage motility in cholestatic liver injury in mice. Sci Rep 2015;5:13423.
96. Ikeda H, Nagashima K, Yanase M, et al. Sphingosine 1-phosphate enhances portal pressure in isolated perfused liver via S1P2 with Rho activation. Biochem Biophys Res Commun 2004;320:754-9.
97. Cao H, Chen L, Zeng Z, et al. Reversal of cholestatic liver disease by the inhibition of sphingosine 1-phosphate receptor 2 signaling. PeerJ 2024;12:e16744.
98. Hong CH, Ko MS, Kim JH, et al. Sphingosine 1-phosphate receptor 4 promotes nonalcoholic steatohepatitis by activating NLRP3 inflammasome. Cell Mol Gastroenterol Hepatol 2022;13:925-47.
99. González-Fernández B, Sánchez DI, Crespo I, et al. Inhibition of the SphK1/S1P signaling pathway by melatonin in mice with liver fibrosis and human hepatic stellate cells. Biofactors 2017;43:272-82.
100. Hada N, Katsume A, Kenichi K, Endo C, Horiba N, Sudoh M. Novel oral SPT inhibitor CH5169356 inhibits hepatic stellate cell activation and ameliorates hepatic fibrosis in mouse models of non-alcoholic steatohepatitis (NASH). Pharmacol Res Perspect 2023;11:e01094.
101. Marrone A, Signoriello E, Alfieri G, et al. Epstein barr virus infection reactivation as a possible trigger of primary biliary cirrhosis-like syndrome in a patient with multiple sclerosis in the course of fingolimod treatment. Infez Med 2014;22:331-6.
102. Li M, Lv Y, Chen F, et al. Co-stimulation of LPAR1 and S1PR1/3 increases the transplantation efficacy of human mesenchymal stem cells in drug-induced and alcoholic liver diseases. Stem Cell Res Ther 2018;9:161.
103. Xu W, Lu C, Zhang F, Shao J, Zheng S. Dihydroartemisinin restricts hepatic stellate cell contraction via an FXR-S1PR2-dependent mechanism. IUBMB Life 2016;68:376-87.
104. Romano A, Friuli M, Del Coco L, et al. Chronic oleoylethanolamide treatment decreases hepatic triacylglycerol level in rat liver by a PPARγ/SREBP-mediated suppression of fatty acid and triacylglycerol synthesis. Nutrients 2021;13:394.
105. Chen L, Li L, Chen J, et al. Oleoylethanolamide, an endogenous PPAR-α ligand, attenuates liver fibrosis targeting hepatic stellate cells. Oncotarget 2015;6:42530-40.
106. Wu HC, Hsieh YR, Wang W, et al. Potential hepatic lipid markers associated with nonalcoholic steatohepatitis and fibrosis in morbid obesity patients. J Clin Med 2023;12:3730.