{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T09:27:38Z","timestamp":1786440458962,"version":"build-2736575974"},"reference-count":84,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are chronic cholestatic liver diseases with limited therapeutic options. First-line therapy for PBC is ursodeoxycholic acid, although up to 40% of patients respond incompletely, and there is no effective therapy for PSC. Newer peroxisome proliferator-activated receptor (PPAR) agonists, e.g., seladelpar and elafibranor, received accelerated FDA approval as second-line treatments for PBC, and additional studies of PPAR agonists for PSC are underway. PPAR agonists have varying affinities for the PPAR isoforms (\u03b1, \u03b4, \u03b3), and the functional effects of isoform activation in humans are less known. Interindividual PPAR isoform expression varies across diseases and traditionally required invasive tissue biopsies for evaluation. Newer experimental approaches, such as extracellular vesicles (EVs) from liquid biopsies, can be used to characterize individual gene expression as an alternative (to tissue biopsy). The transcriptomic profiling of EVs uniquely allows for the quantification of coding and non-coding RNA transcripts, which may be used to study pathways relevant to PPAR expression and regulation and to identify biomarkers of treatment response to PPAR agonists in cholestasis. This review explores the application(s) of liquid biopsy-derived EVs for the identification of PPAR regulated pathways and its potential role in the treatment of PBC and PSC.<\/jats:p>","DOI":"10.3390\/cells15161442","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T08:09:36Z","timestamp":1786435776000},"page":"1442","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeting PPAR-Regulated Pathways to Treat Cholestatic Liver Diseases: Novel Applications of Liquid Biopsies"],"prefix":"10.3390","volume":"15","author":[{"given":"Colleen M.","family":"Hayes","sequence":"first","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Avedisian Hall #395M, 7 Greenhouse Road, Kingston, RI 02881, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniella R.","family":"Cross","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Avedisian Hall #395M, 7 Greenhouse Road, Kingston, RI 02881, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2595-5626","authenticated-orcid":false,"given":"Brahim","family":"Achour","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Avedisian Hall #395M, 7 Greenhouse Road, Kingston, RI 02881, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4724-0576","authenticated-orcid":false,"given":"Nisanne S.","family":"Ghonem","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Avedisian Hall #395M, 7 Greenhouse Road, Kingston, RI 02881, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1053\/j.gastro.2010.09.004","article-title":"Pathogenesis of cholestatic liver disease and therapeutic approaches","volume":"139","author":"Hirschfield","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_2","first-page":"e90780","article-title":"Bile acids initiate cholestatic liver injury by triggering a hepatocyte-specific inflammatory response","volume":"2","author":"Cai","year":"2017","journal-title":"J. Clin. Investig. Insight"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1053\/j.gastro.2009.01.003","article-title":"Improved prognosis of patients with primary biliary cirrhosis that have a biochemical response to ursodeoxycholic acid","volume":"136","author":"Kuiper","year":"2009","journal-title":"Gastroenterology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e0612","DOI":"10.1097\/HC9.0000000000000612","article-title":"PPAR agonists for the treatment of cholestatic liver diseases: Over a decade of clinical progress","volume":"9","author":"Hayes","year":"2025","journal-title":"Hepatol. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1002\/cpt.1930","article-title":"Fenofibrate Improves Liver Function and Reduces the Toxicity of the Bile Acid Pool in Patients with Primary Biliary Cholangitis and Primary Sclerosing Cholangitis Who Are Partial Responders to Ursodiol","volume":"108","author":"Ghonem","year":"2020","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1002\/hep.27744","article-title":"Fibrates and cholestasis","volume":"62","author":"Ghonem","year":"2015","journal-title":"Hepatology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1257","DOI":"10.1124\/mol.104.005389","article-title":"Regulation of human hepatic hydroxysteroid sulfotransferase gene expression by the peroxisome proliferator-activated receptor alpha transcription factor","volume":"67","author":"Fang","year":"2005","journal-title":"Mol. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Gallucci, G.M., Hayes, C.M., Boyer, J.L., Barbier, O., Assis, D.N., and Ghonem, N.S. (2024). PPAR-Mediated Bile Acid Glucuronidation: Therapeutic Targets for the Treatment of Cholestatic Liver Diseases. Cells, 13.","DOI":"10.3390\/cells13151296"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"117303","DOI":"10.1016\/j.biopha.2024.117303","article-title":"PPARbeta\/delta attenuates hepatic fibrosis by reducing SMAD3 phosphorylation and p300 levels via AMPK in hepatic stellate cells","volume":"179","author":"Zhang","year":"2024","journal-title":"Biomed. Pharmacother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1002\/hep.27297","article-title":"The transrepressive activity of peroxisome proliferator-activated receptor alpha is necessary and sufficient to prevent liver fibrosis in mice","volume":"60","author":"Pawlak","year":"2014","journal-title":"Hepatology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1186\/2045-3701-2-34","article-title":"GW501516-activated PPARbeta\/delta promotes liver fibrosis via p38-JNK MAPK-induced hepatic stellate cell proliferation","volume":"2","author":"Kostadinova","year":"2012","journal-title":"Cell Biosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"11392","DOI":"10.1074\/jbc.M310284200","article-title":"Peroxisome proliferator-activated receptor gamma induces a phenotypic switch from activated to quiescent hepatic stellate cells","volume":"279","author":"Hazra","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2570","DOI":"10.1007\/s10753-022-01713-1","article-title":"Fenofibrate Downregulates NF-kappaB Signaling to Inhibit Pro-inflammatory Cytokine Secretion in Human THP-1 Macrophages and During Primary Biliary Cholangitis","volume":"45","author":"Gallucci","year":"2022","journal-title":"Inflammation"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5033","DOI":"10.1093\/nar\/gkv331","article-title":"The transcriptional PPARbeta\/delta network in human macrophages defines a unique agonist-induced activation state","volume":"43","author":"Adhikary","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.1038\/nature05894","article-title":"Macrophage-specific PPARgamma controls alternative activation and improves insulin resistance","volume":"447","author":"Odegaard","year":"2007","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1016\/j.cgh.2020.07.032","article-title":"Inter- and Intra-individual Variation, and Limited Prognostic Utility, of Serum Alkaline Phosphatase in a Trial of Patients With Primary Sclerosing Cholangitis","volume":"19","author":"Trivedi","year":"2021","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"100328","DOI":"10.1016\/j.jhepr.2021.100328","article-title":"Fluctuating biomarkers in primary sclerosing cholangitis: A longitudinal comparison of alkaline phosphatase, liver stiffness, and ELF","volume":"3","author":"Fossdal","year":"2021","journal-title":"JHEP Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jhep.2025.10.022","article-title":"Phase II clinical trials in primary sclerosing cholangitis: Making the most of every opportunity?","volume":"84","author":"Assis","year":"2025","journal-title":"J. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1021\/jm990554g","article-title":"The PPARs: From orphan receptors to drug discovery","volume":"43","author":"Willson","year":"2000","journal-title":"J. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1002\/cpt.1328","article-title":"From Endogenous Compounds as Biomarkers to Plasma-Derived Nanovesicles as Liquid Biopsy; Has the Golden Age of Translational Pharmacokinetics-Absorption, Distribution, Metabolism, Excretion-Drug-Drug Interaction Science Finally Arrived?","volume":"105","author":"Rodrigues","year":"2019","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1002\/cpt.2102","article-title":"Liquid Biopsy Enables Quantification of the Abundance and Interindividual Variability of Hepatic Enzymes and Transporters","volume":"109","author":"Achour","year":"2021","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1124\/dmd.121.000411","article-title":"Role of Extracellular Vesicle-Derived Biomarkers in Drug Metabolism and Disposition","volume":"49","author":"Useckaite","year":"2021","journal-title":"Drug Metab. Dispos."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"27066","DOI":"10.3402\/jev.v4.27066","article-title":"Biological properties of extracellular vesicles and their physiological functions","volume":"4","author":"Siljander","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.1002\/cpt.2576","article-title":"Liquid Biopsy for Patient Characterization in Cardiovascular Disease: Verification against Markers of Cytochrome P450 and P-Glycoprotein Activities","volume":"111","author":"Achour","year":"2022","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1111\/bcp.13793","article-title":"Plasma extracellular nanovesicle (exosome)-derived biomarkers for drug metabolism pathways: A novel approach to characterize variability in drug exposure","volume":"85","author":"Rowland","year":"2019","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"117244","DOI":"10.1016\/j.jpba.2025.117244","article-title":"A liquid biopsy-RNAseq method for monitoring the expression of genes involved in drug disposition: Proof-of-concept application to cholestatic liver disease","volume":"269","author":"Dahal","year":"2026","journal-title":"J. Pharm. Biomed. Anal."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1002\/cpt.2244","article-title":"Exploring the Use of Serum-Derived Small Extracellular Vesicles as Liquid Biopsy to Study the Induction of Hepatic Cytochromes P450 and Organic Anion Transporting Polypeptides","volume":"110","author":"Rodrigues","year":"2021","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1002\/anie.201005969","article-title":"Genome-wide correlation between mRNA and protein in a single cell","volume":"50","author":"Yeung","year":"2011","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Chen, Y., Bian, S., and Le, J. (2025). Molecular Landscape and Diagnostic Model of MASH: Transcriptomic, Proteomic, Metabolomic, and Lipidomic Perspectives. Genes, 16.","DOI":"10.3390\/genes16040399"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1186\/s12967-024-05029-6","article-title":"Multi-omics approaches for drug-response characterization in primary biliary cholangitis and autoimmune hepatitis variant syndrome","volume":"22","author":"Yang","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Lapitz, A., Arbelaiz, A., O\u2019Rourke, C.J., Lavin, J.L., Casta, A., Ibarra, C., Jimeno, J.P., Santos-Laso, A., Izquierdo-Sanchez, L., and Krawczyk, M. (2020). Patients with Cholangiocarcinoma Present Specific RNA Profiles in Serum and Urine Extracellular Vesicles Mirroring the Tumor Expression: Novel Liquid Biopsy Biomarkers for Disease Diagnosis. Cells, 9.","DOI":"10.3390\/cells9030721"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.1159\/000492507","article-title":"Identification of Potential Prognostic Long Non-Coding RNA Biomarkers for Predicting Survival in Patients with Hepatocellular Carcinoma","volume":"48","author":"Liao","year":"2018","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Shigehara, K., Yokomuro, S., Ishibashi, O., Mizuguchi, Y., Arima, Y., Kawahigashi, Y., Kanda, T., Akagi, I., Tajiri, T., and Yoshida, H. (2011). Real-time PCR-based analysis of the human bile microRNAome identifies miR-9 as a potential diagnostic biomarker for biliary tract cancer. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0023584"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1002\/cpt.3291","article-title":"Dealing With Variable Drug Exposure Due to Variable Hepatic Metabolism: A Proof-of-Concept Application of Liquid Biopsy in Renal Impairment","volume":"116","author":"Yee","year":"2024","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/cmi.2015.86","article-title":"The modulation of co-stimulatory molecules by circulating exosomes in primary biliary cirrhosis","volume":"14","author":"Tomiyama","year":"2017","journal-title":"Cell. Mol. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Gan, M., Shen, L., Fan, Y., Tan, Y., Zheng, T., Tang, G., Niu, L., Zhao, Y., Chen, L., and Jiang, D. (2019). MicroRNA-451 and Genistein Ameliorate Nonalcoholic Steatohepatitis in Mice. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20236084"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1186\/s12967-025-06286-9","article-title":"MiR-451a attenuates hepatic steatosis and hepatitis C virus replication by targeting glycerol kinase","volume":"23","author":"Majumdar","year":"2025","journal-title":"J. Transl. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e18428","DOI":"10.7717\/peerj.18428","article-title":"CAF-derived miR-642a-3p supports migration, invasion, and EMT of hepatocellular carcinoma cells by targeting SERPINE1","volume":"12","author":"Zhang","year":"2024","journal-title":"PeerJ"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"110795","DOI":"10.1016\/j.ygeno.2024.110795","article-title":"HSCs-derived exosomes regulate the levels of inflammatory cytokines in HIBECs through miR-122-5p mediated p38 MAPK signaling pathway","volume":"116","author":"Zhang","year":"2024","journal-title":"Genomics"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Chen, R., Yang, X., Qian, L., Shen, B., and Shuai, Z. (2025). HSC-derived exosomal miR-122-5p inhibits EMT and fibrosis of intrahepatic biliary epithelial cells to alleviate primary biliary cholangitis. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1684064"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e70146","DOI":"10.1002\/jsp2.70146","article-title":"Unveiling the Potential Mechanism of Asymmetric Fat Infiltration in Paraspinal Muscles of Adult Degenerative Scoliosis: The Role of the Hsa_circ_0006156\/miR-122-5p\/PPARA Regulatory Network","volume":"8","author":"Yang","year":"2025","journal-title":"JOR Spine"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"110060","DOI":"10.1016\/j.intimp.2023.110060","article-title":"Hepatocyte-derived extracellular vesicles miR-122-5p promotes hepatic ischemia reperfusion injury by regulating Kupffer cell polarization","volume":"119","author":"Liu","year":"2023","journal-title":"Int. Immunopharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jhep.2023.02.027","article-title":"Liquid biopsy-based protein biomarkers for risk prediction, early diagnosis, and prognostication of cholangiocarcinoma","volume":"79","author":"Lapitz","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1002\/hep.29291","article-title":"Serum extracellular vesicles contain protein biomarkers for primary sclerosing cholangitis and cholangiocarcinoma","volume":"66","author":"Arbelaiz","year":"2017","journal-title":"Hepatology"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1038\/s41598-022-06809-0","article-title":"Protein and miRNA profile of circulating extracellular vesicles in patients with primary sclerosing cholangitis","volume":"12","author":"Povero","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1097\/HEP.0000000000001080","article-title":"Immunobiology of primary sclerosing cholangitis","volume":"82","author":"Cornillet","year":"2025","journal-title":"Hepatology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1093\/intimm\/dxy056","article-title":"Ficolin-1 is a promising therapeutic target for autoimmune diseases","volume":"31","author":"Katayama","year":"2019","journal-title":"Int. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4049\/jimmunol.1900868","article-title":"CD13\/Aminopeptidase N Is a Potential Therapeutic Target for Inflammatory Disorders","volume":"204","author":"Lu","year":"2020","journal-title":"J. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Liu, Y., Munker, S., Mullenbach, R., and Weng, H.L. (2012). IL-13 Signaling in Liver Fibrogenesis. Front. Immunol., 3.","DOI":"10.3389\/fimmu.2012.00116"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1053\/j.gastro.2010.03.052","article-title":"Toll-like receptor 9 promotes steatohepatitis by induction of interleukin-1\u03b2 in mice","volume":"139","author":"Miura","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.cytogfr.2006.08.001","article-title":"Endothelial monocyte-activating polypeptide-II and its functions in (patho)physiological processes","volume":"17","author":"Eggermont","year":"2006","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Li, Z., Ju, X., Silveira, P.A., Abadir, E., Hsu, W.H., Hart, D.N.J., and Clark, G.J. (2019). CD83: Activation Marker for Antigen Presenting Cells and Its Therapeutic Potential. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.01312"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1097\/FPC.0b013e328351a486","article-title":"Rare PPARA variants and extreme response to fenofibrate in the Genetics of Lipid-Lowering Drugs and Diet Network Study","volume":"22","author":"Irvin","year":"2012","journal-title":"Pharmacogenet. Genom."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"312","DOI":"10.1038\/tpj.2012.9","article-title":"The PPAR alpha gene is associated with triglyceride, low-density cholesterol and inflammation marker response to fenofibrate intervention: The GOLDN study","volume":"13","author":"Ordovas","year":"2013","journal-title":"Pharmacogenom. J."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Adamowicz, M., Kempinska-Podhorodecka, A., Abramczyk, J., Banales, J.M., Milkiewicz, P., and Milkiewicz, M. (2022). Suppression of Hepatic PPARalpha in Primary Biliary Cholangitis Is Modulated by miR-155. Cells, 11.","DOI":"10.3390\/cells11182880"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Ma, Y., Lu, L., Tan, K., Li, Z., Guo, T., Wu, Y., Wu, W., Zheng, L., Fan, F., and Mo, J. (2022). Reduced peroxisome proliferator-activated receptor-alpha and bile acid nuclear receptor NR1H4\/FXR may affect the hepatic immune microenvironment of biliary atresia. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.875593"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e0140","DOI":"10.1097\/HC9.0000000000000140","article-title":"Circulating cell-free messenger RNA secretome characterization of primary sclerosing cholangitis","volume":"7","author":"Chalasani","year":"2023","journal-title":"Hepatol. Commun."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.jhep.2015.02.019","article-title":"PPARalpha gene expression correlates with severity and histological treatment response in patients with non-alcoholic steatohepatitis","volume":"63","author":"Francque","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2035","DOI":"10.1002\/hep4.1787","article-title":"Adjunct Fenofibrate Up-regulates Bile Acid Glucuronidation and Improves Treatment Response for Patients with Cholestasis","volume":"5","author":"Gallucci","year":"2021","journal-title":"Hepatol. Commun."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2171","DOI":"10.1056\/NEJMoa1714519","article-title":"A Placebo-Controlled Trial of Bezafibrate in Primary Biliary Cholangitis","volume":"378","author":"Corpechot","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1097\/HEP.0000000000000395","article-title":"Seladelpar efficacy and safety at 3 months in patients with primary biliary cholangitis: ENHANCE, a phase 3, randomized, placebo-controlled study","volume":"78","author":"Hirschfield","year":"2023","journal-title":"Hepatology"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1056\/NEJMoa2306185","article-title":"Efficacy and Safety of Elafibranor in Primary Biliary Cholangitis","volume":"390","author":"Kowdley","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.jhep.2025.04.025","article-title":"Safety and efficacy of elafibranor in primary sclerosing cholangitis: The ELMWOOD phase II randomized-controlled trial","volume":"84","author":"Levy","year":"2025","journal-title":"J. Hepatol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2467","DOI":"10.1007\/s11095-011-0473-y","article-title":"PPAR\u03b1 Is Regulated by miR-21 and miR-27b in Human Liver","volume":"28","author":"Kida","year":"2011","journal-title":"Pharm. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1002\/art.39485","article-title":"In Vivo Therapeutic Success of MicroRNA-155 Antagomir in a Mouse Model of Lupus Alveolar Hemorrhage","volume":"68","author":"Zhou","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"e70472","DOI":"10.7554\/eLife.70472","article-title":"Hepatic MIR20B promotes nonalcoholic fatty liver disease by suppressing PPARA","volume":"10","author":"Lee","year":"2021","journal-title":"eLife"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Drakaki, A., Hatziapostolou, M., Polytarchou, C., Vorvis, C., Poultsides, G.A., Souglakos, J., Georgoulias, V., and Iliopoulos, D. (2015). Functional microRNA high throughput screening reveals miR-9 as a central regulator of liver oncogenesis by affecting the PPARA-CDH1 pathway. BMC Cancer, 15.","DOI":"10.1186\/s12885-015-1562-9"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1158\/0008-5472.CAN-14-1192","article-title":"Long Noncoding RNA HULC Modulates Abnormal Lipid Metabolism in Hepatoma Cells through an miR-9\u2013Mediated RXRA Signaling Pathway","volume":"75","author":"Cui","year":"2015","journal-title":"Cancer Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"12519","DOI":"10.3892\/mmr.2021.12519","article-title":"lncRNA MEG3 modulates hepatic stellate cell activation by sponging miR-145 to regulate PPAR\u03b3","volume":"25","author":"Qin","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"BSR20181722","DOI":"10.1042\/BSR20181722","article-title":"LncRNA-H19 promotes hepatic lipogenesis by directly regulating miR-130a\/PPAR\u03b3 axis in non-alcoholic fatty liver disease","volume":"39","author":"Liu","year":"2019","journal-title":"Biosci. Rep."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"117572","DOI":"10.1016\/j.lfs.2020.117572","article-title":"Peroxisome proliferator-activated receptor \u03b3 inhibits hepatic stellate cell activation regulated by miR-942 in chronic hepatitis B liver fibrosis","volume":"253","author":"Tao","year":"2020","journal-title":"Life Sci."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.1136\/gutjnl-2014-308883","article-title":"Liver microRNA-21 is overexpressed in non-alcoholic steatohepatitis and contributes to the disease in experimental models by inhibiting PPAR\u03b1 expression","volume":"65","author":"Loyer","year":"2016","journal-title":"Gut"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Kempi\u0144ska-Podhorodecka, A., Abramczyk, J., Cielica, E., Hu\u0142a, B., Maciejowska, H., Banales, J., Milkiewicz, P., and Milkiewicz, M. (2023). Effect of Low Testosterone Levels on the Expression of Proliferator-Activated Receptor Alpha in Female Patients with Primary Biliary Cholangitis. Cells, 12.","DOI":"10.3390\/cells12182273"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.tig.2015.09.002","article-title":"miRNA Nomenclature: A View Incorporating Genetic Origins, Biosynthetic Pathways, and Sequence Variants","volume":"31","author":"Desvignes","year":"2015","journal-title":"Trends Genet."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e2792","DOI":"10.1038\/cddis.2017.10","article-title":"MiR-130a-3p attenuates activation and induces apoptosis of hepatic stellate cells in nonalcoholic fibrosing steatohepatitis by directly targeting TGFBR1 and TGFBR2","volume":"8","author":"Wang","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1042\/CS20100387","article-title":"Enhanced expression of pro-inflammatory mediators and liver X-receptor-regulated lipogenic genes in non-alcoholic fatty liver disease and hepatitis C","volume":"120","author":"Olcoz","year":"2011","journal-title":"Clin. Sci."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Xiang, J., Deng, Y.-Y., Liu, H.-X., and Pu, Y. (2022). LncRNA MALAT1 Promotes PPAR\u03b1\/CD36-Mediated Hepatic Lipogenesis in Nonalcoholic Fatty Liver Disease by Modulating miR-206\/ARNT Axis. Front. Bioeng. Biotechnol., 10.","DOI":"10.3389\/fbioe.2022.858558"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1186\/s13578-022-00910-7","article-title":"RNA binding protein HuR protects against NAFLD by suppressing long noncoding RNA H19 expression","volume":"12","author":"Wang","year":"2022","journal-title":"Cell Biosci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s12986-021-00557-0","article-title":"The long noncoding RNA MALAT1 modulates adipose loss in cancer-associated cachexia by suppressing adipogenesis through PPAR-\u03b3","volume":"18","author":"Han","year":"2021","journal-title":"Nutr. Metab."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"5012","DOI":"10.21037\/tcr-2025-1372","article-title":"The functional role of exosomal miRNA-675-3p derived from patients with hepatocellular carcinoma","volume":"14","author":"Liang","year":"2025","journal-title":"Transl. Cancer Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e2300631","DOI":"10.1002\/ardp.202300631","article-title":"Exosomal miR-122, miR-128, miR-200, miR-298, and miR-342 as novel diagnostic biomarkers in NAFL\/NASH: Impact of LPS\/TLR-4\/FoxO3 pathway","volume":"357","author":"Samy","year":"2024","journal-title":"Arch. Pharm."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1053\/j.gastro.2006.08.026","article-title":"Characterization of HULC, a novel gene with striking up-regulation in hepatocellular carcinoma, as noncoding RNA","volume":"132","author":"Panzitt","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1002\/bcp.70453","article-title":"Evaluation of cytochrome P450 (CYP) induction using RT-qPCR in exosomes isolated from plasma samples: Method development and qualification","volume":"92","author":"Xu","year":"2026","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1074\/mcp.M113.036095","article-title":"Targeted peptide measurements in biology and medicine: Best practices for mass spectrometry-based assay development using a fit-for-purpose approach","volume":"13","author":"Carr","year":"2014","journal-title":"Mol. Cell. Proteom."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/16\/1442\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T08:29:31Z","timestamp":1786436971000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/15\/16\/1442"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,11]]},"references-count":84,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["cells15161442"],"URL":"https:\/\/doi.org\/10.3390\/cells15161442","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,11]]}}}