{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T10:18:25Z","timestamp":1788257905956,"version":"build-2803163510"},"reference-count":91,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by fatty liver, inflammation, and fibrosis, which eventually results in hepatocarcinoma. Recently, MASH therapeutics have been approved by the FDA; however, options remain limited, and the discovery of additional molecular targets is ongoing. The prolyl isomerase Pin1 regulates the function of phosphorylated substrates by converting the cis-trans form of proline. Pin1 interacts with specific substrates in each organ and controls lipid and energy metabolism through modulating the localization and stabilization of target proteins. Interestingly, a high-calorie diet upregulates Pin1 expression in the liver and adipocytes. It suppresses fatty acid oxidation, thermogenesis, and lipolysis by regulating PPAR\u03b1, PRDM16, and adipose triglyceride lipase, which ultimately leads to steatosis. Beyond metabolic dysregulation, Pin1 is essential for activating hepatic stellate cells, which cause liver fibrosis. Pin1 conditional knockout mice exhibit resistance to high-calorie diet-induced MASH, which indicates a role for Pin1 in multiple organs as a central regulator linking metabolic dysfunction to liver inflammation and fibrosis. These results suggest that Pin1 inhibitors may be effective for MASH treatment. In this review, we discuss the roles of Pin1 in MASH development and as a potential therapy target.<\/jats:p>","DOI":"10.3390\/ijms27177788","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:48:36Z","timestamp":1788256116000},"page":"7788","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Effect of Prolyl Isomerase Pin1 on the Development of Metabolic Dysfunction-Associated Steatohepatitis and a New Treatment Strategy"],"prefix":"10.3390","volume":"27","author":[{"given":"Yasuka","family":"Matsunaga","sequence":"first","affiliation":[{"name":"John W. Deming Department of Medicine, Tulane University School of Medicine, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3482-8710","authenticated-orcid":false,"given":"Masa-Ki","family":"Inoue","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Machi","family":"Kanna","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, Faculty of Engineering, Sanyo-Onoda City University, Daigakudori 1-1-1, Sanyo-Onoda 756-0884, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoichiro","family":"Asano","sequence":"additional","affiliation":[{"name":"Department of Biomedical Chemistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Nakatsu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Chemistry, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8553, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1097\/HEP.0000000000000323","article-title":"AASLD Practice Guidance on the Clinical Assessment and Management of Nonalcoholic Fatty Liver Disease","volume":"77","author":"Rinella","year":"2023","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global Epidemiology of Nonalcoholic Fatty Liver Disease\u2014Meta-Analytic Assessment of Prevalence, Incidence, and Outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1097\/HEP.0000000000000004","article-title":"The Global Epidemiology of Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH): A Systematic Review","volume":"77","author":"Younossi","year":"2023","journal-title":"Hepatology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1002\/hep.29085","article-title":"Increased Risk of Mortality by Fibrosis Stage in Nonalcoholic Fatty Liver Disease: Systematic Review and Meta-Analysis","volume":"65","author":"Dulai","year":"2017","journal-title":"Hepatology"},{"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":"572","DOI":"10.1038\/nrendo.2017.80","article-title":"Regulation of Hepatic Glucose Metabolism in Health and Disease","volume":"13","author":"Petersen","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1016\/j.cell.2021.04.015","article-title":"Mechanisms and Disease Consequences of Nonalcoholic Fatty Liver Disease","volume":"184","author":"Loomba","year":"2021","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3990","DOI":"10.1172\/JCI129187","article-title":"Altered Adipose Tissue and Adipocyte Function in the Pathogenesis of Metabolic Syndrome","volume":"129","author":"Kahn","year":"2019","journal-title":"J. Clin. Investig."},{"key":"ref_9","first-page":"815","article-title":"Mechanism of Metabolic Dysfunction-Associated Steatotic Liver Disease: Important Role of Lipid Metabolism","volume":"12","author":"Feng","year":"2024","journal-title":"J. Clin. Transl. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/S0016-5085(98)70599-2","article-title":"Steatohepatitis: A Tale of Two \u201cHits\u201d?","volume":"114","author":"Day","year":"1998","journal-title":"Gastroenterology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1836","DOI":"10.1002\/hep.24001","article-title":"Evolution of Inflammation in Nonalcoholic Fatty Liver Disease: The Multiple Parallel Hits Hypothesis","volume":"52","author":"Tilg","year":"2010","journal-title":"Hepatology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1053\/j.gastro.2015.04.005","article-title":"Weight Loss Through Lifestyle Modification Significantly Reduces Features of Nonalcoholic Steatohepatitis","volume":"149","author":"Friedman","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1016\/j.cgh.2021.01.023","article-title":"Weight Loss and Weight Regain in Usual Clinical Practice: Results from the TARGET-NASH Observational Cohort","volume":"20","author":"Malespin","year":"2022","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1056\/NEJMoa2309000","article-title":"A Phase 3, Randomized, Controlled Trial of Resmetirom in NASH with Liver Fibrosis","volume":"390","author":"Harrison","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1056\/NEJMoa2413258","article-title":"Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis","volume":"392","author":"Sanyal","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1056\/NEJMoa2028395","article-title":"A Placebo-Controlled Trial of Subcutaneous Semaglutide in Nonalcoholic Steatohepatitis","volume":"384","author":"Newsome","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/S2468-1253(23)00068-7","article-title":"Semaglutide 2.4 mg Once Weekly in Patients with Non-Alcoholic Steatohepatitis-Related Cirrhosis: A Randomised, Placebo-Controlled Phase 2 Trial","volume":"8","author":"Loomba","year":"2023","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1038\/380544a0","article-title":"A Human Peptidyl-Prolyl Isomerase Essential for Regulation of Mitosis","volume":"380","author":"Lu","year":"1996","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1126\/science.283.5406.1325","article-title":"Function of WW Domains as Phosphoserine- or Phosphothreonine-Binding Modules","volume":"283","author":"Lu","year":"1999","journal-title":"Science"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"eadi8743","DOI":"10.1126\/scisignal.adi8743","article-title":"Pin1-Catalyzed Conformational Regulation after Phosphorylation: A Distinct Checkpoint in Cell Signaling and Drug Discovery","volume":"17","author":"Lu","year":"2024","journal-title":"Sci. Signal."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3951","DOI":"10.1158\/0008-5472.CAN-12-4360","article-title":"SENP1 DeSUMOylates and Regulates Pin1 Protein Activity and Cellular Function","volume":"73","author":"Chen","year":"2013","journal-title":"Cancer Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"36575","DOI":"10.1074\/jbc.M504548200","article-title":"Polo-Like Kinase 1-Mediated Phosphorylation Stabilizes Pin1 by Inhibiting Its Ubiquitination in Human Cells","volume":"280","author":"Eckerdt","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.molcel.2011.03.005","article-title":"Death-Associated Protein Kinase 1 Phosphorylates Pin1 and Inhibits Its Prolyl Isomerase Activity and Cellular Function","volume":"42","author":"Lee","year":"2011","journal-title":"Mol. Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2561","DOI":"10.1002\/hep.31983","article-title":"Phosphorylation and Stabilization of PIN1 by JNK Promote Intrahepatic Cholangiocarcinoma Growth","volume":"74","author":"Lepore","year":"2021","journal-title":"Hepatology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1038\/s41467-023-44349-x","article-title":"Stabilization of Pin1 by USP34 Promotes Ubc9 Isomerization and Protein Sumoylation in Glioma Stem Cells","volume":"15","author":"Zhu","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8149","DOI":"10.1073\/pnas.1200804109","article-title":"Mixed-Lineage Kinase 3 Phosphorylates Prolyl Isomerase Pin1 to Regulate Its Nuclear Translocation and Cellular Function","volume":"109","author":"Rangasamy","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.canlet.2019.10.043","article-title":"Prolyl Isomerase Pin1 in Metabolic Reprogramming of Cancer Cells","volume":"470","author":"Nakatsu","year":"2020","journal-title":"Cancer Lett."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e2507711122","DOI":"10.1073\/pnas.2507711122","article-title":"Programmable Immunoprobiotics Orchestrate Antitumor Immune Response with Pin1 Inhibition for Pancreatic Cancer Treatment","volume":"122","author":"Yuan","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1158\/2159-8290.CD-24-0866","article-title":"PIN1 Prolyl Isomerase Promotes Initiation and Progression of Bladder Cancer through the SREBP2-Mediated Cholesterol Biosynthesis Pathway","volume":"15","author":"Wang","year":"2025","journal-title":"Cancer Discov."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"168087","DOI":"10.1016\/j.bbadis.2025.168087","article-title":"Pin1 Mediates Metabolic Dysfunction-Associated Steatohepatitis in Mice Fed High-Fat, High-Cholesterol Diet by Regulating Both PPAR\u03b1 and Acetyl-CoA Carboxylase","volume":"1872","author":"Nakatsu","year":"2026","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"154459","DOI":"10.1016\/j.metabol.2020.154459","article-title":"Prolyl Isomerase Pin1 Interacts with Adipose Triglyceride Lipase and Negatively Controls Both Its Expression and Lipolysis","volume":"115","author":"Nakatsu","year":"2021","journal-title":"Metabolism"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3221","DOI":"10.1016\/j.celrep.2019.02.066","article-title":"Prolyl Isomerase Pin1 Suppresses Thermogenic Programs in Adipocytes by Promoting Degradation of Transcriptional Co-Activator PRDM16","volume":"26","author":"Nakatsu","year":"2019","journal-title":"Cell Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"44526","DOI":"10.1074\/jbc.M112.397133","article-title":"Role of Pin1 Protein in the Pathogenesis of Nonalcoholic Steatohepatitis in a Rodent Model","volume":"287","author":"Nakatsu","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Jin, Y., Shangguan, Z., Pang, J., Chen, Y., Lin, S., and Liu, H. (2024). Pin1 Exacerbates Non-Alcoholic Fatty Liver Disease by Enhancing Its Activity through Binding to ACC1. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25115822"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"11886","DOI":"10.1074\/jbc.M117.780726","article-title":"The Prolyl Isomerase Pin1 Increases \u03b2-Cell Proliferation and Enhances Insulin Secretion","volume":"292","author":"Nakatsu","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Kanna, M., Nakatsu, Y., Yamamotoya, T., Kushiyama, A., Fujishiro, M., Sakoda, H., Ono, H., Arihiro, K., and Asano, T. (2023). Hepatic Pin1 Expression, Particularly in Nuclei, Is Increased in NASH Patients in Accordance with Evidence of the Role of Pin1 in Lipid Accumulation Shown in Hepatoma Cell Lines. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24108847"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1159\/000365415","article-title":"Can Serum Pin1 Level Be Regarded as an Indicative Marker of Nonalcoholic Steatohepatitis and Fibrotic Stages?","volume":"90","author":"Cengiz","year":"2014","journal-title":"Digestion"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"100014","DOI":"10.1016\/j.metop.2019.100014","article-title":"PIN1, a Perspective on Genetic Biomarker for Nonalcoholic Fatty Liver Disease (NAFLD)","volume":"3","author":"Wang","year":"2019","journal-title":"Metabol. Open"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1093\/eurheartj\/ehu179","article-title":"Targeting Prolyl Isomerase Pin1 Prevents Mitochondrial Oxidative Stress and Vascular Dysfunction: Insights in Patients with Diabetes","volume":"36","author":"Paneni","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1007\/s40618-022-01812-8","article-title":"Circulating Levels of PIN1 and Glucose Metabolism in Young People with Obesity","volume":"45","author":"Bianchi","year":"2022","journal-title":"J. Endocrinol. Investig."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e186427","DOI":"10.1172\/JCI186420","article-title":"MASH: The Nexus of Metabolism, Inflammation, and Fibrosis","volume":"135","author":"Steinberg","year":"2025","journal-title":"J. Clin. Investig."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.18632\/oncotarget.26691","article-title":"Prolyl Isomerase Pin1 Binds to and Stabilizes Acetyl-CoA Carboxylase 1 Protein, Thereby Supporting Cancer Cell Proliferation","volume":"10","author":"Ueda","year":"2019","journal-title":"Oncotarget"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/j.cmet.2010.04.005","article-title":"Defective Hepatic Autophagy in Obesity Promotes ER Stress and Causes Insulin Resistance","volume":"11","author":"Yang","year":"2010","journal-title":"Cell Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/nrm3311","article-title":"AMPK: A Nutrient and Energy Sensor That Maintains Energy Homeostasis","volume":"13","author":"Hardie","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"24255","DOI":"10.1074\/jbc.M115.658559","article-title":"Prolyl Isomerase Pin1 Negatively Regulates AMP-Activated Protein Kinase (AMPK) by Associating with the CBS Domain in the Gamma Subunit","volume":"290","author":"Nakatsu","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/s41467-022-28201-2","article-title":"Depletion of Mitochondrial Methionine Adenosyltransferase Alpha1 Triggers Mitochondrial Dysfunction in Alcohol-Associated Liver Disease","volume":"13","author":"Murray","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.1002\/hep.26226","article-title":"Mitochondrial Adaptations and Dysfunctions in Nonalcoholic Fatty Liver Disease","volume":"58","author":"Begriche","year":"2013","journal-title":"Hepatology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.cmet.2007.12.009","article-title":"Selective versus Total Insulin Resistance: A Pathogenic Paradox","volume":"7","author":"Brown","year":"2008","journal-title":"Cell Metab."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3459","DOI":"10.1093\/emboj\/20.13.3459","article-title":"Pin1 Is Overexpressed in Breast Cancer and Cooperates with Ras Signaling in Increasing the Transcriptional Activity of c-Jun towards Cyclin D1","volume":"20","author":"Wulf","year":"2001","journal-title":"EMBO J."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"20812","DOI":"10.1074\/jbc.M110.206904","article-title":"Peptidyl-prolyl cis\/trans isomerase NIMA-interacting 1 associates with insulin receptor substrate-1 and enhances insulin actions and adipogenesis","volume":"286","author":"Nakatsu","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"102870","DOI":"10.1016\/j.redox.2023.102870","article-title":"TNF\u03b1 is a key trigger of inflammation in diet-induced non-obese MASLD in mice","volume":"66","author":"Burger","year":"2023","journal-title":"Redox. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1038\/s41423-025-01310-w","article-title":"NF-kappaB in inflammation and cancer","volume":"22","author":"Mao","year":"2025","journal-title":"Cell. Mol. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1038\/nri.2017.52","article-title":"The non-canonical NF-kappaB pathway in immunity and inflammation","volume":"17","author":"Sun","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1016\/S1097-2765(03)00490-8","article-title":"Regulation of NF-kappaB signaling by Pin1-dependent prolyl isomerization and ubiquitin-mediated proteolysis of p65\/RelA","volume":"12","author":"Ryo","year":"2003","journal-title":"Mol. Cell."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e12816","DOI":"10.1111\/cpr.12816","article-title":"Pin1 promotes pancreatic cancer progression and metastasis by activation of NF-kappaB-IL-18 feedback loop","volume":"53","author":"Sun","year":"2020","journal-title":"Cell Prolif."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1093\/carcin\/bgp027","article-title":"The prolyl isomerase Pin1 interacts with a ribosomal protein S6 kinase to enhance insulin-induced AP-1 activity and cellular transformation","volume":"30","author":"Lee","year":"2009","journal-title":"Carcinogenesis"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Dong, R., Xue, Z., Fan, G., Zhang, N., Wang, C., Li, G., and Da, Y. (2021). Pin1 Promotes NLRP3 Inflammasome Activation by Phosphorylation of p38 MAPK Pathway in Septic Shock. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.620238"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/S2213-8587(24)00318-8","article-title":"Metabolic dysfunction-associated steatotic liver disease: Heterogeneous pathomechanisms and effectiveness of metabolism-based treatment","volume":"13","author":"Stefan","year":"2025","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.mce.2016.07.030","article-title":"Pin1 Enhances Adipocyte Differentiation by Positively Regulating the Transcriptional Activity of PPAR\u03b3","volume":"436","author":"Han","year":"2016","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1038\/ncb2629","article-title":"ERK1\/2-Dependent Phosphorylation and Nuclear Translocation of PKM2 Promotes the Warburg Effect","volume":"14","author":"Yang","year":"2012","journal-title":"Nat. Cell Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.1021\/pr401292p","article-title":"Proteome Profiling of Mitotic Clonal Expansion during 3T3-L1 Adipocyte Differentiation Using iTRAQ-2DLC-MS\/MS","volume":"13","author":"Jiang","year":"2014","journal-title":"J. Proteome Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1369\/0022155415627681","article-title":"TGF-\u03b2\/SMAD Pathway and Its Regulation in Hepatic Fibrosis","volume":"64","author":"Xu","year":"2016","journal-title":"J. Histochem. Cytochem."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.cbi.2018.07.008","article-title":"New Insights into TGF-\u03b2\/Smad Signaling in Tissue Fibrosis","volume":"292","author":"Hu","year":"2018","journal-title":"Chem.-Biol. Interact."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1016\/j.jhep.2014.02.004","article-title":"Pin1 Induction in the Fibrotic Liver and Its Roles in TGF-\u03b21 Expression and Smad2\/3 Phosphorylation","volume":"60","author":"Yang","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"113544","DOI":"10.1016\/j.yexcr.2023.113544","article-title":"Prolyl Isomerase Pin1 Promotes Extracellular Matrix Production in Hepatic Stellate Cells through Regulating Formation of the Smad3-TAZ Complex","volume":"425","author":"Aoyama","year":"2023","journal-title":"Exp. Cell Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"23294","DOI":"10.1074\/jbc.M111.313684","article-title":"Pin1 Protein Regulates Smad Protein Signaling and Pulmonary Fibrosis","volume":"287","author":"Shen","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.ccell.2016.10.001","article-title":"ERK Activation Globally Downregulates miRNAs through Phosphorylating Exportin-5","volume":"30","author":"Sun","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_68","first-page":"479","article-title":"Pin1 Regulates TGF-\u03b21 Production by Activated Human and Murine Eosinophils and Contributes to Allergic Lung Fibrosis","volume":"118","author":"Shen","year":"2008","journal-title":"J. Clin. Investig."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1016\/j.jhep.2011.07.010","article-title":"A Role for Autophagy during Hepatic Stellate Cell Activation","volume":"55","author":"Thoen","year":"2011","journal-title":"J. Hepatol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"110940","DOI":"10.1016\/j.cellsig.2023.110940","article-title":"Prolyl Isomerase Pin1 Promotes Autophagy and Cancer Cell Viability through Activating FoxO3 Signalling","volume":"113","author":"Long","year":"2024","journal-title":"Cell. Signal."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/j.jhep.2020.04.037","article-title":"Acetyl-CoA Carboxylase Inhibition Disrupts Metabolic Reprogramming during Hepatic Stellate Cell Activation","volume":"73","author":"Bates","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.canlet.2018.12.010","article-title":"Pin1 Inhibition Reverses the Acquired Resistance of Human Hepatocellular Carcinoma Cells to Regorafenib via the Gli1\/Snail\/E-Cadherin Pathway","volume":"444","author":"Wang","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"702","DOI":"10.1016\/j.ijcard.2015.10.221","article-title":"Pin1 Inhibitor Juglone Prevents Diabetic Vascular Dysfunction","volume":"203","author":"Costantino","year":"2016","journal-title":"Int. J. Cardiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1016\/j.ejphar.2015.05.005","article-title":"Epigallocatechin Gallate Attenuated Non-Alcoholic Steatohepatitis Induced by Methionine- and Choline-Deficient Diet","volume":"761","author":"Ding","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"5953","DOI":"10.1021\/bi973162p","article-title":"Selective Inactivation of Parvulin-Like Peptidyl-Prolyl cis\/trans Isomerases by Juglone","volume":"37","author":"Hennig","year":"1998","journal-title":"Biochemistry"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.fct.2012.01.002","article-title":"Juglone, from Juglans mandshurica Maxim, Inhibits Growth and Induces Apoptosis in Human Leukemia Cell HL-60 through a Reactive Oxygen Species-Dependent Mechanism","volume":"50","author":"Xu","year":"2012","journal-title":"Food Chem. Toxicol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"156298","DOI":"10.1016\/j.prp.2025.156298","article-title":"EGCG Inhibits Hepatic Stellate Cell Activity and Liver Fibrosis by Targeting the MDM2\/MUC5AC-Mediated TGF-\u03b21\/Smad Signaling Pathway","volume":"277","author":"Yang","year":"2026","journal-title":"Pathol. Res. Pract."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1158\/1940-6207.CAPR-11-0301","article-title":"Epigallocatechin Gallate Suppresses Tumorigenesis by Directly Targeting Pin1","volume":"4","author":"Urusova","year":"2011","journal-title":"Cancer Prev. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/nsmb743","article-title":"A Receptor for Green Tea Polyphenol EGCG","volume":"11","author":"Tachibana","year":"2004","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1038\/nm.3839","article-title":"Active Pin1 Is a Key Target of All-Trans Retinoic Acid in Acute Promyelocytic Leukemia and Breast Cancer","volume":"21","author":"Wei","year":"2015","journal-title":"Nat. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.cmet.2019.11.013","article-title":"Macrophage MerTK Promotes Liver Fibrosis in Nonalcoholic Steatohepatitis","volume":"31","author":"Cai","year":"2020","journal-title":"Cell Metab."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"3069","DOI":"10.1038\/s41467-018-05402-2","article-title":"Arsenic Targets Pin1 and Cooperates with Retinoic Acid to Inhibit Cancer-Driving Pathways and Tumor-Initiating Cells","volume":"9","author":"Kozono","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1002\/hep.29819","article-title":"Targeting Pin1 by Inhibitor API-1 Regulates MicroRNA Biogenesis and Suppresses Hepatocellular Carcinoma Development","volume":"68","author":"Pu","year":"2018","journal-title":"Hepatology"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"4704","DOI":"10.7150\/thno.34588","article-title":"MicroRNA Biogenesis Is Enhanced by Liposome-Encapsulated Pin1 Inhibitor in Hepatocellular Carcinoma","volume":"9","author":"Sun","year":"2019","journal-title":"Theranostics"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"15772","DOI":"10.1038\/ncomms15772","article-title":"A Covalent PIN1 Inhibitor Selectively Targets Cancer Cells by a Dual Mechanism of Action","volume":"8","author":"Campaner","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1038\/s41573-021-00371-6","article-title":"PROTAC targeted protein degraders: The past is prologue","volume":"21","author":"Langley","year":"2022","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_87","doi-asserted-by":"crossref","unstructured":"Ma, Y., Teng, Y., Liu, J., Deng, Y., Xu, L., Gao, R., Peng, T., Li, W., Wei, Y., and Li, L. (2026). Systematic Optimization of Proteolysis-Targeting Chimeras for PIN1 Enables Selective Degradation and Antitumor Activity In Vivo. Pharmaceutics, 18.","DOI":"10.3390\/pharmaceutics18030288"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"5027","DOI":"10.1039\/D3SC06558H","article-title":"Discovery of Potent PROTAC Degraders of Pin1 for the Treatment of Acute Myeloid Leukemia","volume":"15","author":"Shi","year":"2024","journal-title":"Chem. Sci."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1038\/21650","article-title":"The Prolyl Isomerase Pin1 Restores the Function of Alzheimer-Associated Phosphorylated Tau Protein","volume":"399","author":"Lu","year":"1999","journal-title":"Nature"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Hoshino, Y., and Uchida, T. (2022). Prolyl Isomerase Pin1 Controls Meiotic Progression in Mouse Oocytes. Cells, 11.","DOI":"10.3390\/cells11233772"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.bbrc.2018.02.090","article-title":"Prolyl Isomerase Pin1 Is Required for Sperm Production by Promoting Mitotic Progression of Spermatogonial Stem Cells","volume":"497","author":"Kamo","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7788\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:56:47Z","timestamp":1788256607000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7788"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,31]]},"references-count":91,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27177788"],"URL":"https:\/\/doi.org\/10.3390\/ijms27177788","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,31]]}}}