The expression of AE2 and its association with autophagy-related markers and senescent markers p16<sup>INK4a</sup> and p21<sup>WAF1/Cip1</sup> were immunohistochemically determined in livers taken from the patients with PBC (n = 50) and 69 control diseased and normal livers.
CDKN1a, up-regulated in high-risk PBC, correlated with significantly increased expression of its gene product, the senescence marker p21<sup>WAF1/Cip</sup>, by biliary epithelial cells.
We examined immunohistochemically the expression of p62 in livers taken from patients with PBC (n = 46) and control livers (n = 78) and its colocalization with microtubule-associated proteins-light chain 3β (LC3), lysosome-associated membrane protein-1 (LAMP-1) and senescent markers (p16(INK) (4a) and p21(WAF) (1/Cip1) ).
In conclusion, oxidative stress-induced p21(WAF1/Cip1) expression in BECs in PBC is closely associated with activation of the ATM pathway and the resultant reduced regeneration or cell cycle arrest of BECs may be related to the progressive loss of small bile ducts of PBC.
Telomere shortening and an accumulation of DNA damage coincide with increased expression of p16(INK4a) and p21(WAF1/Cip1) in the damaged bile ducts, characterize biliary cellular senescence, and may play a role in the following progressive bile duct loss in PBC.