Autophagy May Precede Cellular Senescence of Bile Ductular Cells in Ductular Reaction in Primary Biliary Cirrhosis

Abstract

Recent studies disclosed that autophagy facilitates the process of senescence. Given that cellular senescence is involved in the pathophysiology of ductular reaction (DR) in primary biliary cirrhosis (PBC), we examined an involvement of autophagy in DRs in PBC and control livers. We examined immunohistochemically the expression of microtubule-associated proteins light chain 3β (LC3) as autophagy marker, p62/sequestosome-1 (p62) as autophagy-related marker in bile ductular cells in livers taken from the patients with PBC (n = 42), and control livers (n = 100). The expression of senescent markers (p16(INK4a) and p21(WAF1/Cip1)) in bile ductular cells and their correlation with autophagy was also evaluated. The expression of LC3 was seen in coarse vesicles in the cytoplasm of bile ductular cells and significantly more frequently in PBC of both early and advanced stages when compared to control livers (p < 0.01). The expression of p62 was seen as intracytoplasmic aggregates and significantly more frequently in PBC when compared to control livers (p < 0.05). The expression of LC3 and p62 significantly correlated with each other (p < 0.01). The expression of LC3 and p62 significantly correlated with the expression of p16(INK4a), p21(WAF1/Cip1) (p < 0.05). Autophagy is frequently seen in bile ductular cells in DRs in PBC. Since cellular senescence of bile ductular cells is rather frequent in the advanced stage of PBC, autophagy may precede cellular senescence of bile ductular cells in DRs in PBC.