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Liver Int. 2013 Feb;33(2):312-20. doi: 10.1111/liv.12049. Epub 2012 Dec 11.

Increased expression of mitochondrial proteins associated with autophagy in biliary epithelial lesions in primary biliary cirrhosis.

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  • 1Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.

Abstract

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.

© 2012 John Wiley & Sons A/S.

PMID:
23231002
[PubMed - indexed for MEDLINE]
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