Primary biliary cholangitis: A tale of epigenetically-induced secretory failure?

• Published in: Journal of hepatology Vol. 69; no. 6; pp. 1371 - 1383
• Main Authors: Rodrigues, Pedro M., Perugorria, Maria J., Santos-Laso, Alvaro, Bujanda, Luis, Beuers, Ulrich, Banales, Jesus M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.12.2018; Elsevier Science Ltd
• Subjects: AE2; Autoantibodies; Bile ducts; Biliary bicarbonate; Biomarkers - metabolism; Chloride-Bicarbonate Antiporters - metabolism; Cholangiocytes; Cholangitis; Cholestasis; Cholestasis - metabolism; Dihydrolipoyllysine-Residue Acetyltransferase - immunology; DNA Methylation; Environment; Environmental factors; Epigenesis, Genetic; Epigenetics; Genetic diversity; Genetic Predisposition to Disease; Humans; Immune response; Liver Cirrhosis, Biliary - genetics; Liver Cirrhosis, Biliary - immunology; Liver Cirrhosis, Biliary - metabolism; Liver diseases; MicroRNAs - genetics; MicroRNAs - metabolism; miR-506; miRNA; Pathogenesis; PBC; Polymorphism, Single Nucleotide; RNA, Long Noncoding - genetics; RNA, Long Noncoding - immunology; PBC; miR-506; Biliary bicarbonate; AE2; Cholangiocytes
• ISSN: 0168-8278; 1600-0641; 1600-0641
• DOI: 10.1016/j.jhep.2018.08.020

Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease associated with autoimmune-related destruction of small to medium size intrahepatic bile ducts. The aetiology of PBC is unknown and its pathogenesis remains obscure. Both genetic variants and environmental factors have been linked to increased PBC susceptibility, with other alterations known to cooperate in disease pathobiology. Increasing evidence indicates the presence of epigenetic abnormalities in PBC, particularly alterations of cholangiocellular microRNAs (miRNAs or miRs). This review highlights and discusses the most relevant epigenetic alterations found in patients with PBC, focusing on the role of miR-506 in the promotion of cholestasis and immune activation.