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Article

Suppression of Hepatic PPARα in Primary Biliary Cholangitis Is Modulated by miR-155

1
Department of Medical Biology, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland
2
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
3
Department of Biochemistry and Genetics, School of Sciences, University of Navarra, 31009 Pamplona, Spain
4
Liver and Internal Medicine Unit, Medical University of Warsaw, 02-097 Warsaw, Poland
5
Translational Medicine Group, Pomeranian Medical University, 70-111 Szczecin, Poland
*
Author to whom correspondence should be addressed.
Academic Editors: Kay-Dietrich Wagner and Nicole Wagner
Cells 2022, 11(18), 2880; https://doi.org/10.3390/cells11182880
Received: 21 July 2022 / Revised: 8 September 2022 / Accepted: 10 September 2022 / Published: 15 September 2022
(This article belongs to the Special Issue The Role of PPARs in Disease II)
Background: PPARα 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 PPARα. Methods: The expression of miR-155, miR-21 and PPARα 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 PPARα 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 PPARα in hepatocytes, whereas, in cholangiocytes, only miR-21 suppressed PPARα. 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 PPARα upregulation. In NHC cells, the expression of miR-21 was induced by LPS but did not affect PPARα expression. Conclusions: Hepatic PPARα 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 PPARα. View Full-Text
Keywords: miRNA; PPARα; liver; primary biliary cholangitis miRNA; PPARα; liver; primary biliary cholangitis
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MDPI and ACS Style

Adamowicz, M.; Kempinska-Podhorodecka, A.; Abramczyk, J.; Banales, J.M.; Milkiewicz, P.; Milkiewicz, M. Suppression of Hepatic PPARα in Primary Biliary Cholangitis Is Modulated by miR-155. Cells 2022, 11, 2880. https://doi.org/10.3390/cells11182880

AMA Style

Adamowicz M, Kempinska-Podhorodecka A, Abramczyk J, Banales JM, Milkiewicz P, Milkiewicz M. Suppression of Hepatic PPARα in Primary Biliary Cholangitis Is Modulated by miR-155. Cells. 2022; 11(18):2880. https://doi.org/10.3390/cells11182880

Chicago/Turabian Style

Adamowicz, Monika, Agnieszka Kempinska-Podhorodecka, Joanna Abramczyk, Jesus M. Banales, Piotr Milkiewicz, and Malgorzata Milkiewicz. 2022. "Suppression of Hepatic PPARα in Primary Biliary Cholangitis Is Modulated by miR-155" Cells 11, no. 18: 2880. https://doi.org/10.3390/cells11182880

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