{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T12:38:40Z","timestamp":1791463120309,"version":"4.3.4"},"reference-count":76,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T00:00:00Z","timestamp":1745366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Liver Sinusoidal Endothelial Cells (LSECs) play a crucial role in maintaining liver homeostasis, regulating immune responses, and fibrosis in liver diseases. This review explores the unique functions of LSECs in liver pathology, particularly their roles in immune tolerance, antigen presentation, and the modulation of hepatic stellate cells (HSCs) during fibrosis. LSECs act as key regulators of immune balance in the liver by preventing excessive immune activation while also filtering antigens and interacting with immune cells, including Kupffer cells and T cells. Metabolic Dysfunction-Associated Fatty Liver Disease(MAFLD) is significant because it can lead to advanced liver dysfunction, such as cirrhosis and liver cancer. The prevalence of Metabolic Associated Steatohepatitis (MASH) is increasing globally, particularly in the United States, and is closely linked to rising rates of obesity and type 2 diabetes. Early diagnosis and intervention are vital to prevent severe outcomes, highlighting the importance of studying LSECs in liver disease. However, during chronic liver diseases, LSECs undergo dysfunction, leading to their capillarization, loss of fenestrations, and promotion of pro-fibrotic signaling pathways such as Transforming growth factor-beta (TGF-\u03b2), which subsequently activates HSCs and contributes to the progression of liver fibrosis. The review also discusses the dynamic interaction between LSECs, HSCs, and other hepatic cells during the progression of liver diseases, emphasizing how changes in LSEC phenotype contribute to liver scarring and fibrosis. Furthermore, it highlights the potential of LSECs as therapeutic targets for modulating immune responses and preventing fibrosis in liver diseases. By restoring LSECs\u2019 function and targeting pathways associated with their dysfunction, novel therapies could be developed to halt or reverse liver disease progression. The findings of this review reinforce the importance of LSECs in liver pathology and suggest that they hold significant promises as targets for future treatment strategies aimed at addressing chronic liver diseases.<\/jats:p>","DOI":"10.3390\/ijms26093988","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T08:26:43Z","timestamp":1745396803000},"page":"3988","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Liver Sinusoidal Endothelial Cells in the Regulation of Immune Responses and Fibrosis in Metabolic Dysfunction-Associated Fatty Liver Disease"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6603-4447","authenticated-orcid":false,"given":"Munish","family":"Puri","sequence":"first","affiliation":[{"name":"Onco-Immunology, Magnit Global, Folsom, CA 95630, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Snehal","family":"Sonawane","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Illinois, Chicago, IL 60612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/s41575-018-0020-y","article-title":"Liver Sinusoidal Endothelial Cells\u2014Gatekeepers of Hepatic Immunity","volume":"15","author":"Shetty","year":"2018","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.jhep.2016.07.009","article-title":"Liver Sinusoidal Endothelial Cells: Physiology and Role in Liver Diseases","volume":"66","author":"Poisson","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1038\/cmi.2016.5","article-title":"Immunological Functions of Liver Sinusoidal Endothelial Cells","volume":"13","author":"Knolle","year":"2016","journal-title":"Cell. Mol. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/nrgastro.2015.200","article-title":"Immunology in the Liver\u2014from Homeostasis to Disease","volume":"13","author":"Heymann","year":"2016","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1002\/hep.29466","article-title":"Modeling the Epidemic of Nonalcoholic Fatty Liver Disease Demonstrates an Exponential Increase in Burden of Disease","volume":"67","author":"Estes","year":"2018","journal-title":"Hepatology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"197","DOI":"10.7570\/jomes23052","article-title":"Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A State-of-the-Art Review","volume":"32","author":"Chan","year":"2023","journal-title":"J. Obes. Metab. Syndr."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Eskridge, W., Cryer, D.R., Schattenberg, J.M., Gastaldelli, A., Malhi, H., Allen, A.M., Noureddin, M., and Sanyal, A.J. (2023). Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Dysfunction-Associated Steatohepatitis: The Patient and Physician Perspective. J. Clin. Med., 12.","DOI":"10.3390\/jcm12196216"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bhandari, S., Larsen, A.K., McCourt, P., Smedsr\u00f8d, B., and S\u00f8rensen, K.K. (2021). The Scavenger Function of Liver Sinusoidal Endothelial Cells in Health and Disease. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.757469"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1172\/JCI88881","article-title":"Liver Inflammation and Fibrosis","volume":"127","author":"Koyama","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/s41575-023-00821-z","article-title":"Friend or Foe? The Elusive Role of Hepatic Stellate Cells in Liver Cancer","volume":"20","author":"Cogliati","year":"2023","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1038\/labinvest.2015.95","article-title":"Pivotal Role of Liver Sinusoidal Endothelial Cells in NAFLD\/NASH Progression","volume":"95","author":"Miyao","year":"2015","journal-title":"Lab. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1861","DOI":"10.1172\/JCI66025","article-title":"Liver Sinusoidal Endothelial Cells and Liver Regeneration","volume":"123","author":"DeLeve","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1038\/s41580-021-00373-7","article-title":"Liver Regeneration and Inflammation: From Fundamental Science to Clinical Applications","volume":"22","author":"Campana","year":"2021","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Wang, X.-K., and Peng, Z.-G. (2021). Targeting Liver Sinusoidal Endothelial Cells: An Attractive Therapeutic Strategy to Control Inflammation in Nonalcoholic Fatty Liver Disease. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.655557"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Du, W., and Wang, L. (2022). The Crosstalk Between Liver Sinusoidal Endothelial Cells and Hepatic Microenvironment in NASH Related Liver Fibrosis. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.936196"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Furuta, K., Guo, Q., Hirsova, P., and Ibrahim, S.H. (2020). Emerging Roles of Liver Sinusoidal Endothelial Cells in Nonalcoholic Steatohepatitis. Biology, 9.","DOI":"10.3390\/biology9110395"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1097\/HEP.0000000000000207","article-title":"The Evolving Role of Liver Sinusoidal Endothelial Cells in Liver Health and Disease","volume":"78","author":"McConnell","year":"2023","journal-title":"Hepatology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/s10456-021-09780-y","article-title":"Angiodiversity and Organotypic Functions of Sinusoidal Endothelial Cells","volume":"24","author":"Koch","year":"2021","journal-title":"Angiogenesis"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mehrfeld, C., Zenner, S., Kornek, M., and Lukacs-Kornek, V. (2018). The Contribution of Non-Professional Antigen-Presenting Cells to Immunity and Tolerance in the Liver. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.00635"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3","DOI":"10.3390\/livers1010002","article-title":"The Space of Disse: The Liver Hub in Health and Disease","volume":"1","author":"Nevzorova","year":"2021","journal-title":"Livers"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Wilkinson, A.L., Qurashi, M., and Shetty, S. (2020). The Role of Sinusoidal Endothelial Cells in the Axis of Inflammation and Cancer Within the Liver. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.00990"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Strauss, O., Phillips, A., Ruggiero, K., Bartlett, A., and Dunbar, P.R. (2017). Immunofluorescence Identifies Distinct Subsets of Endothelial Cells in the Human Liver. Sci. Rep., 7.","DOI":"10.1038\/srep44356"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/j.jhep.2013.12.025","article-title":"Macrophage Heterogeneity in Liver Injury and Fibrosis","volume":"60","author":"Tacke","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1002\/hep.31790","article-title":"Macrophage Heterogeneity in NASH: More Than Just Nomenclature","volume":"74","author":"Parthasarathy","year":"2021","journal-title":"Hepatology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1002\/hep.27376","article-title":"Liver Sinusoidal Endothelial Cells in Hepatic Fibrosis","volume":"61","author":"DeLeve","year":"2015","journal-title":"Hepatology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1016\/j.dld.2021.07.006","article-title":"Intercellular Crosstalk of Liver Sinusoidal Endothelial Cells in Liver Fibrosis, Cirrhosis and Hepatocellular Carcinoma","volume":"54","author":"Li","year":"2022","journal-title":"Dig. Liver Dis."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Szafranska, K., Kruse, L.D., Holte, C.F., McCourt, P., and Zapotoczny, B. (2021). The wHole Story About Fenestrations in LSEC. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.735573"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1186\/s12964-024-01720-9","article-title":"Role of Liver Sinusoidal Endothelial Cell in Metabolic Dysfunction-Associated Fatty Liver Disease","volume":"22","author":"He","year":"2024","journal-title":"Cell Commun. Signal."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1093\/intimm\/dxac030","article-title":"Liver Cirrhosis and Immune Dysfunction","volume":"34","author":"Hasa","year":"2022","journal-title":"Int. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2803","DOI":"10.1007\/s11033-021-06269-1","article-title":"Liver Sinusoidal Endothelial Cells Are Implicated in Multiple Fibrotic Mechanisms","volume":"48","author":"Ma","year":"2021","journal-title":"Mol. Biol. Rep."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Tian, S.-P., Ge, J.-Y., Song, Y.-M., Yu, X.-Q., Chen, W.-H., Chen, Y.-Y., Ye, D., and Zheng, Y.-W. (2024). A Novel Efficient Strategy to Generate Liver Sinusoidal Endothelial Cells from Human Pluripotent Stem Cells. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-64195-1"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/cmi.2015.112","article-title":"Modulation of Liver Tolerance by Conventional and Nonconventional Antigen-Presenting Cells and Regulatory Immune Cells","volume":"13","author":"Horst","year":"2016","journal-title":"Cell Mol. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1038\/82161","article-title":"Efficient Presentation of Exogenous Antigen by Liver Endothelial Cells to CD8+ T Cells Results in Antigen-Specific T-Cell Tolerance","volume":"6","author":"Limmer","year":"2000","journal-title":"Nat. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1007\/s10875-008-9251-y","article-title":"TGF-\u03b2 and Regulatory T Cell in Immunity and Autoimmunity","volume":"28","author":"Wan","year":"2008","journal-title":"J. Clin. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1038\/ni.2691","article-title":"Immune Surveillance by the Liver","volume":"14","author":"Jenne","year":"2013","journal-title":"Nat. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1002\/hep.27332","article-title":"Hepatic Inflammation and Fibrosis: Functional Links and Key Pathways","volume":"61","author":"Seki","year":"2015","journal-title":"Hepatology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7666","DOI":"10.3748\/wjg.v23.i43.7666","article-title":"Pathological Process of Liver Sinusoidal Endothelial Cells in Liver Diseases","volume":"23","author":"Ni","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"303","DOI":"10.3350\/cmh.2024.0022","article-title":"Liver Sinusoidal Endothelial Cell: An Important yet Often Overlooked Player in the Liver Fibrosis","volume":"30","author":"Qu","year":"2024","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3892\/mmr.2024.13164","article-title":"Liver Sinusoidal Endothelial Cells as Potential Drivers of Liver Fibrosis (Review)","volume":"29","author":"Gao","year":"2024","journal-title":"Mol. Med. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"111556","DOI":"10.1016\/j.fct.2020.111556","article-title":"The Liver Fibrosis Niche: Novel Insights into the Interplay between Fibrosis-Composing Mesenchymal Cells, Immune Cells, Endothelial Cells, and Extracellular Matrix","volume":"143","author":"Matsuda","year":"2020","journal-title":"Food Chem. Toxicol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Ruan, B., Duan, J.-L., Xu, H., Tao, K.-S., Han, H., Dou, G.-R., and Wang, L. (2021). Capillarized Liver Sinusoidal Endothelial Cells Undergo Partial Endothelial-Mesenchymal Transition to Actively Deposit Sinusoidal ECM in Liver Fibrosis. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.671081"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Akk\u0131z, H., Gieseler, R.K., and Canbay, A. (2024). Liver Fibrosis: From Basic Science towards Clinical Progress, Focusing on the Central Role of Hepatic Stellate Cells. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202405.1666.v1"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"377","DOI":"10.4254\/wjh.v7.i3.377","article-title":"Angiogenesis and Liver Fibrosis","volume":"7","author":"Elpek","year":"2015","journal-title":"World J. Hepatol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Allameh, A., Niayesh-Mehr, R., Aliarab, A., Sebastiani, G., and Pantopoulos, K. (2023). Oxidative Stress in Liver Pathophysiology and Disease. Antioxidants, 12.","DOI":"10.3390\/antiox12091653"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Pei, Q., Yi, Q., and Tang, L. (2023). Liver Fibrosis Resolution: From Molecular Mechanisms to Therapeutic Opportunities. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119671"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1055\/s-0037-1617455","article-title":"Liver Sinusoidal Endothelial Cell: An Update","volume":"37","author":"DeLeve","year":"2017","journal-title":"Semin. Liver Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"e22125","DOI":"10.1096\/fj.202101426R","article-title":"Endothelial Dysfunction in Pathological Processes of Chronic Liver Disease during Aging","volume":"36","author":"Wan","year":"2022","journal-title":"FASEB J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"10512","DOI":"10.3748\/wjg.v22.i48.10512","article-title":"Liver Fibrosis and Hepatic Stellate Cells: Etiology, Pathological Hallmarks and Therapeutic Targets","volume":"22","author":"Zhang","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"673","DOI":"10.3350\/cmh.2024.0343","article-title":"Unlocking the Role of Liver Sinusoidal Endothelial Cells: Key Players in Liver Fibrosis: Editorial on \u201cLiver Sinusoidal Endothelial Cell: An Important yet Often Overlooked Player in the Liver Fibrosis\u201d","volume":"30","author":"Iwakiri","year":"2024","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_50","first-page":"208","article-title":"Spatial Computational Hepatic Molecular Biomarker Reveals LSEC Role in Midlobular Liver Zonation Fibrosis in DILI and NASH Liver Injury","volume":"4","author":"Puri","year":"2024","journal-title":"Int. J. Transl. Med."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Czyzynska-Cichon, I., Kotlinowski, J., Blacharczyk, O., Giergiel, M., Szymanowski, K., Metwally, S., Wojnar-Lason, K., Dobosz, E., Koziel, J., and Lekka, M. (2024). Early and Late Phases of Liver Sinusoidal Endothelial Cell (LSEC) Defenestration in Mouse Model of Systemic Inflammation. Cell. Mol. Biol. Lett., 29.","DOI":"10.1186\/s11658-024-00655-w"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e230026","DOI":"10.1530\/JME-23-0026","article-title":"RISING STARS: Liver Sinusoidal Endothelial Transcription Factors in Metabolic Homeostasis and Disease","volume":"71","author":"Nagy","year":"2023","journal-title":"J. Mol. Endocrinol."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Soydemir, S., Comella, O., Abdelmottaleb, D., and Pritchett, J. (2020). Does Mechanocrine Signaling by Liver Sinusoidal Endothelial Cells Offer New Opportunities for the Development of Anti-Fibrotics?. Front. Med., 6.","DOI":"10.3389\/fmed.2019.00312"},{"key":"ref_54","first-page":"386","article-title":"Immunomodulatory Effects of Transforming Growth Factor-\u03b2 in the Liver","volume":"3","author":"Schon","year":"2014","journal-title":"Hepatobiliary Surg. Nutr."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1002\/hep.27268","article-title":"Emerging Roles of Notch Signaling in Liver Disease","volume":"61","author":"Geisler","year":"2015","journal-title":"Hepatology"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Lurje, I., Hammerich, L., and Tacke, F. (2020). Dendritic Cell and T Cell Crosstalk in Liver Fibrogenesis and Hepatocarcinogenesis: Implications for Prevention and Therapy of Liver Cancer. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21197378"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"100023","DOI":"10.1016\/j.crphar.2021.100023","article-title":"Effects of Cytokine Signaling Inhibition on Inflammation-Driven Tissue Remodeling","volume":"2","author":"Bignold","year":"2021","journal-title":"Curr. Res. Pharmacol. Drug Discov."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Bravo, M., Raurell, I., Hide, D., Fern\u00e1ndez-Iglesias, A., Gil, M., Barber\u00e1, A., Salcedo, M.T., Augustin, S., Genesc\u00e0, J., and Martell, M. (2019). Restoration of Liver Sinusoidal Cell Phenotypes by Statins Improves Portal Hypertension and Histology in Rats with NASH. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-56366-2"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1186\/s12964-022-00838-y","article-title":"Cancer Combination Therapies by Angiogenesis Inhibitors; a Comprehensive Review","volume":"20","author":"Ansari","year":"2022","journal-title":"Cell Commun. Signal."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Duan, S., Li, X., Fan, G., and Liu, R. (2022). Targeting Bile Acid Signaling for the Treatment of Liver Diseases: From Bench to Bed. Biomed. Pharmacother., 152.","DOI":"10.1016\/j.biopha.2022.113154"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1042\/CS20190249","article-title":"Application of Nintedanib and Other Potential Anti-Fibrotic Agents in Fibrotic Diseases","volume":"133","author":"Liu","year":"2019","journal-title":"Clin. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"5060","DOI":"10.1073\/pnas.0511167103","article-title":"Galectin-3 Regulates Myofibroblast Activation and Hepatic Fibrosis","volume":"103","author":"Henderson","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"SE211","DOI":"10.4052\/tigg.1744.1SE","article-title":"Clinical Trials and Applications of Galectin Antagonists","volume":"30","author":"Girard","year":"2018","journal-title":"Trends Glycosci. Glycotechnol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1186\/s13287-022-03041-5","article-title":"Stem Cells for Treatment of Liver Fibrosis\/Cirrhosis: Clinical Progress and Therapeutic Potential","volume":"13","author":"Liu","year":"2022","journal-title":"Stem Cell Res. Ther."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/s11010-020-03903-7","article-title":"The Effect of Aging on VEGF\/VEGFR2 Signal Pathway Genes Expression in Rat Liver Sinusoidal Endothelial Cell","volume":"476","author":"Wang","year":"2021","journal-title":"Mol. Cell. Biochem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1111\/imm.13298","article-title":"Nanoparticle-Mediated Targeting of Autoantigen Peptide to Cross-Presenting Liver Sinusoidal Endothelial Cells Protects from CD8 T-Cell-Driven Autoimmune Cholangitis","volume":"162","author":"Carambia","year":"2021","journal-title":"Immunology"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Jouve, M., Carpentier, R., Kraiem, S., Legrand, N., and Sobolewski, C. (2023). MiRNAs in Alcohol-Related Liver Diseases and Hepatocellular Carcinoma: A Step toward New Therapeutic Approaches?. Cancers, 15.","DOI":"10.3390\/cancers15235557"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Jangra, A., Kothari, A., Sarma, P., Medhi, B., Omar, B.J., and Kaushal, K. (2022). Recent Advancements in Antifibrotic Therapies for Regression of Liver Fibrosis. Cells, 11.","DOI":"10.3390\/cells11091500"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"100722","DOI":"10.1016\/j.jhepr.2023.100722","article-title":"Increased Sinusoidal Pressure Impairs Liver Endothelial Mechanosensing, Uncovering Novel Biomarkers of Portal Hypertension","volume":"5","author":"Magaz","year":"2023","journal-title":"JHEP Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/s41392-022-01070-3","article-title":"Targeting Fibrosis: Mechanisms and Clinical Trials","volume":"7","author":"Zhao","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"S15","DOI":"10.1016\/j.jhep.2015.02.039","article-title":"Hepatic Fibrosis: Concept to Treatment","volume":"62","author":"Trautwein","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1089\/adt.2019.919","article-title":"Automated Machine Learning Diagnostic Support System as a Computational Biomarker for Detecting Drug-Induced Liver Injury Patterns in Whole Slide Liver Pathology Images","volume":"18","author":"Puri","year":"2020","journal-title":"ASSAY Drug Dev. Technol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"100779","DOI":"10.1016\/j.crmeth.2024.100779","article-title":"Bioengineering Methods for Vascularizing Organoids","volume":"4","author":"Nwokoye","year":"2024","journal-title":"Cell Rep. Methods"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.pbiomolbio.2023.08.002","article-title":"Computational Approaches for Modeling and Structural Design of Biological Systems: A Comprehensive Review","volume":"185","author":"Gayathiri","year":"2023","journal-title":"Prog Biophys. Mol. Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.jcmgh.2022.11.008","article-title":"In Vitro Models for the Study of Liver Biology and Diseases: Advances and Limitations","volume":"15","author":"Kaur","year":"2022","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Antunes, N., Kundu, B., Kundu, S.C., Reis, R.L., and Correlo, V. (2022). In Vitro Cancer Models: A Closer Look at Limitations on Translation. 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