{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:36:45Z","timestamp":1787027805199,"version":"build-2736575974"},"reference-count":56,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T00:00:00Z","timestamp":1663200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004569","name":"Program of Polish Minister of Science and Higher Education \u201cRegional Initiative of Excellence\u201d in 2019\u20132022","doi-asserted-by":"publisher","award":["002\/RID\/2018\/19"],"award-info":[{"award-number":["002\/RID\/2018\/19"]}],"id":[{"id":"10.13039\/501100004569","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: PPAR\u03b1 is a ligand-activated transcription factor that shows protective effects against metabolic disorders, inflammation and apoptosis. Primary biliary cholangitis and primary sclerosing cholangitis result in the intrahepatic accumulation of bile acids that leads to liver dysfunction and damage. Small, non-coding RNAs such as miR-155 and miR-21 are associated with silencing PPAR\u03b1. Methods: The expression of miR-155, miR-21 and PPAR\u03b1 were evaluated using real-time PCR on liver tissue, as well as on human hepatocytes (HepG2) or cholangiocytes (NHCs) following exposure to lipopolysaccharide (LPS), glycodeoxycholic acid (GCDCA), lithocholic acid (LCA) and\/or ursodeoxycholic acid (UDCA). Results: A reduction of PPAR\u03b1 in primary biliary cholangitis (PBC) livers was associated with miR-21 and miR-155 upregulation. Experimental overexpression of either miR-155 or miR-21 inhibited PPAR\u03b1 in hepatocytes, whereas, in cholangiocytes, only miR-21 suppressed PPAR\u03b1. Both GCDCA and LCA induced the cell type-specific upregulation of miR-155 or miR-21. In HepG2, LPS-induced miR-155 expression was blocked by a cotreatment with UDCA and was associated with PPAR\u03b1 upregulation. In NHC cells, the expression of miR-21 was induced by LPS but did not affect PPAR\u03b1 expression. Conclusions: Hepatic PPAR\u03b1 expression is reduced in PBC livers as a likely result of miR-155 overexpression. UDCA effectively reduced both baseline and LPS-induced miR-155 expression, thus preventing the suppression of PPAR\u03b1.<\/jats:p>","DOI":"10.3390\/cells11182880","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T22:11:10Z","timestamp":1663279870000},"page":"2880","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Suppression of Hepatic PPAR\u03b1 in Primary Biliary Cholangitis Is Modulated by miR-155"],"prefix":"10.3390","volume":"11","author":[{"given":"Monika","family":"Adamowicz","sequence":"first","affiliation":[{"name":"Department of Medical Biology, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7513-8640","authenticated-orcid":false,"given":"Agnieszka","family":"Kempinska-Podhorodecka","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Abramczyk","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesus M.","family":"Banales","sequence":"additional","affiliation":[{"name":"Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute, Donostia University Hospital, University of the Basque Country (UPV\/EHU), CIBERehd, Ikerbasque, 20014 San Sebastian, Spain"},{"name":"Department of Biochemistry and Genetics, School of Sciences, University of Navarra, 31009 Pamplona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Milkiewicz","sequence":"additional","affiliation":[{"name":"Liver and Internal Medicine Unit, Medical University of Warsaw, 02-097 Warsaw, Poland"},{"name":"Translational Medicine Group, Pomeranian Medical University, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2064-0545","authenticated-orcid":false,"given":"Malgorzata","family":"Milkiewicz","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1016\/S0140-6736(20)31607-X","article-title":"Primary biliary cholangitis","volume":"396","author":"Lleo","year":"2020","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1002\/hep.22428","article-title":"Biochemical response to ursodeoxycholic acid and long-term prognosis in primary biliary cirrhosis","volume":"48","author":"Corpechot","year":"2008","journal-title":"Hepatology"},{"key":"ref_3","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_4","doi-asserted-by":"crossref","first-page":"154338","DOI":"10.1016\/j.metabol.2020.154338","article-title":"The role of peroxisome proliferator-activated receptors (PPAR) in immune responses","volume":"114","author":"Christofides","year":"2021","journal-title":"Metabolism"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"15401","DOI":"10.1073\/pnas.1307211110","article-title":"Pathogenic role of diabetes-induced PPAR-+- down-regulation in microvascular dysfunction","volume":"110","author":"Hu","year":"2013","journal-title":"Proc. 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