Liver international : official journal of the International Association for the Study of the Liver · 2012
Increased expression of mitochondrial proteins associated with autophagy in biliary epithelial lesions in primary biliary cirrhosis.
Сравнительное исследованиеСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Sasaki Motoko, Miyakoshi Masami, Sato Yasunori, Nakanuma Yasuni
Аннотация
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 (LC3), 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 LC3, p62 and LAMP-1 and the cell-surface expression of PDC-E2 in cultured biliary epithelial cells (BECs) treated with various stresses.
RESULTS: Intense granular expression of PDC-E2 and CCO was seen in the damaged small bile ducts (SBDs) 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 LC3 in damaged SBDs in PBC. The accumulation of LC3-expressing punctae colocalized with PDC-E2 and CCO was significantly more increased in cultured BECs treated with various stresses. The cell-surface expression of PDC-E2 was induced by various stresses in BECs.
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.
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 (LC3), 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 LC3, p62 and LAMP-1 and the cell-surface expression of PDC-E2 in cultured biliary epithelial cells (BECs) treated with various stresses.
RESULTS: Intense granular expression of PDC-E2 and CCO was seen in the damaged small bile ducts (SBDs) 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 LC3 in damaged SBDs in PBC. The accumulation of LC3-expressing punctae colocalized with PDC-E2 and CCO was significantly more increased in cultured BECs treated with various stresses. The cell-surface expression of PDC-E2 was induced by various stresses in BECs.
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.