Frequent cellular senescence in small bile ducts in primary biliary cirrhosis: a possible role in bile duct loss
Frequent cellular senescence in small bile ducts in primary biliary cirrhosis: a possible role in bile duct loss
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DOI：
10.1002/path.1729
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发表时间：
2005-03-01
影响因子：
7.3
通讯作者：
Nakanuma, Y
中科院分区：
文献类型：
--
作者：
Sasaki, M;Ikeda, H;Nakanuma, Y
原发性胆汁性肝硬化中进行性胆管丧失的发病机制仍不清楚。在这项研究中，对原发性胆汁性肝硬化患者 (n = 33) 的肝组织样本中胆管上皮细胞细胞衰老的参与情况进行了检查，并与对照患病肝脏和正常肝脏 (n = 83) 进行了比较。此外，培养的小鼠胆管上皮细胞中的氧化应激可诱导细胞衰老。原发性胆汁性肝硬化的小胆管中的胆管上皮细胞，尤其是慢性非化脓性胆管炎患者的胆管上皮细胞，经常表达衰老相关的β-半乳糖苷酶以及衰老相关的p16（INK4）和p21（WAF1/CIP）。相反，衰老相关标记物很少在对照肝脏的小胆管中表达。早期PBC中髓过氧化物酶阳性炎症细胞向胆管上皮细胞层的浸润与胆管上皮细胞的细胞衰老密切相关。培养的小鼠胆管上皮细胞的细胞衰老是通过 p38MAPK 依赖性途径用 H2O2 处理诱导的，并且一氧化氮增强了 H2O2 诱导的细胞衰老。氧化应激和一氧化氮介导的细胞衰老可能与胆管病变有关，随后在原发性胆汁性肝硬化中出现进行性胆管丧失。版权所有 (C) 2005 大不列颠及爱尔兰病理学会。由约翰·威利父子有限公司出版
The pathogenesis of progressive bile duct loss in primary biliary cirrhosis remains unclear. In this study, the involvement of cellular senescence of biliary epithelial cells was examined in liver tissue samples from patients with primary biliary cirrhosis (n = 33), and compared with control diseased and normal livers (n = 83). In addition, cellular senescence was induced by oxidative stress in cultured mouse biliary epithelial cells. Biliary epithelial cells in small bile ducts in primary biliary cirrhosis, especially those in patients presenting with chronic non-suppurative cholangitis, frequently expressed senescence-associated beta-galactosidase, and senescence-associated p16(INK4) and p21(WAF1/CIP). In contrast, senescence-associated markers were rarely expressed in small bile ducts in control livers. The infiltration of myeloperoxidase-positive inflammatory cells into biliary epithelial cell layers was closely associated with the cellular senescence of biliary epithelial cells in early-stage PBC. Cellular senescence of cultured mouse biliary epithelial cells was induced by treatment with H2O2 via the p38MAPK-dependent pathway and nitric oxide-augmented H2O2-induced cellular senescence. Oxidative stress- and nitric oxide-mediated cellular senescence may be involved in bile duct lesions, which are followed by progressive bile duct loss in primary biliary cirrhosis. Copyright (C) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.