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Increased expression of mitochondrial proteins associated with autophagy in biliary epithelial lesions in primary biliary cirrhosis
Author(s) -
Sasaki Motoko,
Miyakoshi Masami,
Sato Yasunori,
Nakanuma Yasuni
Publication year - 2013
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12049
Subject(s) - autophagy , primary biliary cirrhosis , colocalization , biology , mitochondrion , immunofluorescence , microbiology and biotechnology , mitophagy , sequestosome 1 , pathology , cancer research , immunology , antibody , apoptosis , medicine , biochemistry
Background/Aims We have reported the involvement of deregulated autophagy and subsequent cellular senescence in biliary epithelial lesions in primary biliary cirrhosis ( PBC ). Given that mitochondria are a major target of autophagy, we hypothesized that deregulated autophagy of mitochondria may be involved in autoimmune pathogenesis in PBC . Methods We examined immunohistochemically the expression of pyruvate dehydrogenase complex‐E2 component ( PDC ‐E2) and cytochrome c oxidase, subunit I ( CCO ), in livers taken from patients with PBC ( n = 42) and control livers ( n = 76). The colocalization of mitochondrial antigens with an autophagy marker microtubule‐associated protein‐light chain 3β ( LC 3), a deregulated autophagy marker p62/sequestosome‐1 (p62) and a lysosomal marker LAMP ‐1 was examined by double immunofluorescence. We examined the colocalization of mitochondrial antigens with LC 3, p62 and LAMP ‐1 and the cell‐surface expression of PDC ‐E2 in cultured biliary epithelial cells ( BEC s) treated with various stresses. Results Intense granular expression of PDC ‐E2 and CCO was seen in the damaged small bile ducts ( SBD s) in PBC and the expression was significantly more frequent in PBC than in control livers ( P < 0.01). The granular expression of mitochondrial antigens was colocalized with LC 3 in damaged SBD s in PBC . The accumulation of LC 3‐expressing punctae colocalized with PDC ‐E2 and CCO was significantly more increased in cultured BEC s treated with various stresses. The cell‐surface expression of PDC ‐E2 was induced by various stresses in BEC s. Conclusion Deregulated autophagy may contribute to the abnormal expression of mitochondrial antigens and may be involved in the autoimmune pathogenesis of bile duct lesions in PBC .