title: In recurrent primary biliary cirrhosis after liver transplantation, biliary epithelial cells show increased expression of mitochondrial proteins.
abstract: In biliary epithelial lesions in primary biliary cirrhosis (PBC), mitochondrial proteins associated with deregulated autophagy are abnormally expressed. We examined whether this could be used as a diagnostic marker for end-stage PBC and recurrent PBC after liver transplantation. We examined the expression of the mitochondrial protein pyruvate dehydrogenase complex-E2 component and cytochrome c oxidase, subunit I (CCO), the autophagy-related marker microtubule-associated protein-light chain 3 (LC3), and p62/sequestosome-1 and the senescence markers p16(Ink4a) and p21(WAF1/Cip1) in small bile ducts and bile ductules in explanted livers from patients with PBC (n = 20) in comparison with liver tissue from control patients (n = 21) and post-transplant samples including recurrent PBC and cellular rejection (n = 28). Intense granular expression of mitochondrial proteins was significantly more frequent in small bile ducts in explanted livers with PBC than in control livers (p < 0.05). Post-transplant samples comprised of three groups: group A (positive for mitochondrial proteins, n = 7), group B (positive for either autophagy-related or senescence markers but negative for mitochondrial proteins, n = 7), and group C (all negative, n = 14). All but one case of group A were clinically and histologically diagnosed as recurrent PBC. In contrast, all cases of group B were diagnosed as cellular rejection. This study suggests that the expression of mitochondrial proteins in small bile ducts may be a useful diagnostic marker for end-stage PBC and recurrent PBC after liver transplantation.
authors.affiliation: Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, 920-8640, Japan. m8sasaki@med.kanazawa-u.ac.jp.
authors.forename: Motoko
authors.initials: M
authors.lastname: Sasaki
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA, 98195, USA.
authors.forename: Maylee
authors.initials: M
authors.lastname: Hsu
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA, 98195, USA.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Yeh
authors.affiliation: Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, 920-8640, Japan.|Division of Pathology, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Yasuni
authors.initials: Y
authors.lastname: Nakanuma
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D001343:Autophagy; D001652:Bile Ducts / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis; D019941:Cyclin-Dependent Kinase Inhibitor p16; D051047:Dihydrolipoyllysine-Residue Acetyltransferase / Q000032:analysis; D003576:Electron Transport Complex IV / Q000032:analysis; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D008105:Liver Cirrhosis, Biliary / Q000175:diagnosis* / Q000378:metabolism; D016031:Liver Transplantation / Q000009:adverse effects*; D024101:Mitochondrial Proteins / Q000032:analysis*; D009363:Neoplasm Proteins / Q000032:analysis; D016601:RNA-Binding Proteins / Q000032:analysis; D012008:Recurrence
chemical_list: D015415:Biomarkers; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D024101:Mitochondrial Proteins; D009363:Neoplasm Proteins; C118585:P62 protein, human; D016601:RNA-Binding Proteins; D003576:Electron Transport Complex IV; C581860:cytochrome c oxidase subunit I, human; D051047:Dihydrolipoyllysine-Residue Acetyltransferase; D000410:Alanine Transaminase
keywords: Autophagy and cellular senescence; Biliary epithelial cell; Post-liver transplant rejection; Primary biliary cirrhosis; Pyruvate dehydrogenase complex-E2 component