Cholangiocyte cilia are abnormal in syndromic and non-syndromic biliary atresia.
Cholangiocyte cilia are abnormal in syndromic and non-syndromic biliary atresia.
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DOI：
10.1038/modpathol.2011.212
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发表时间：
2012-05
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影响因子：
--
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中科院分区：
文献类型：
--
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胆道闭锁是一种新生儿疾病，以侵袭性纤维炎性胆道闭塞为特征。大约20%的胆道闭锁患者表现出左右偏侧的缺陷(综合征性胆道闭锁)。纤毛参与了胆管细胞的重要生理功能，由于一些纤毛病变与偏侧缺陷和肝纤维化有关，我们推测综合征性胆道闭锁患者表现出破坏胆管细胞动态平衡的胆管细胞纤毛异常。研究对象为9例胆道闭锁标本，其中7例为开塞前诊断活检，2例为肝移植。5个标本来自偏侧缺损者。这些指标与正常的儿科肝脏以及受原发性硬化性胆管炎、肝豆状核变性和心绞痛影响的肝脏进行了比较。活检切片用抗角蛋白19(胆管细胞标记物)和乙酰化α微管蛋白(纤毛标记物)的抗体染色，并用共聚焦显微镜观察。计算机辅助相对定量用于比较不同样本胆管内纤毛的染色情况。令人惊讶的是，与正常肝脏和疾病对照组相比，胆道闭锁标本中的纤毛明显较短，取向异常，且数量较少，无论是否存在偏侧缺陷。与正常肝脏和其他胆汁淤积性疾病影响的肝脏相比，综合征性和非综合征性胆道闭锁肝脏的胆管细胞纤毛均有明显的异常。虽然这可能是由严重的胆汁淤积或炎症引起的，但它也可能反映了不同形式胆道闭锁的共同机制，并可能对了解疾病的进展具有重要意义。
Biliary atresia is a neonatal disorder characterized by aggressive fibroinflammatory obliteration of the biliary tract. Approximately 20 percent of biliary atresia patients demonstrate left-right laterality defects (syndromic biliary atresia). Cilia participate in important physiologic functions in cholangiocytes, and since some ciliopathies have been associated with both laterality defects and hepatic fibrosis, we hypothesized that patients with syndromic biliary atresia exhibit abnormalities of cholangiocyte cilia that disrupt cholangiocyte homeostasis. Nine biliary atresia specimens were studied, including pre-Kasai diagnostic biopsies (n=7) and liver explants (n=2). Five specimens were from patients with laterality defects. These were compared to normal pediatric livers as well as livers affected by primary sclerosing cholangitis, Wilson’s disease, and cardiac cirrhosis. Biopsy sections were stained with antibodies against keratin 19 (a cholangiocyte marker) and acetylated α-tubulin (a cilia marker) and were visualized by confocal microscopy. Computer-assisted relative quantification was used to compare staining of cilia within bile ducts among samples. Surprisingly, cilia in biliary atresia specimens were significantly shorter, abnormal in their orientation, and less abundant compared to normal liver and disease controls regardless of the presence of a laterality defect. There are significant abnormalities of cholangiocyte cilia in both syndromic and non-syndromic biliary atresia livers compared to normal livers and livers affected by other cholestatic diseases. While this may result from severe cholestasis or inflammation, it may also reflect common mechanistic pathways in different forms of biliary atresia and may have important implications for understanding the progression of the disease.
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影响因子：
2.1
作者：
Simms RJ;Hynes AM;Eley L;Sayer JA
通讯作者：
Sayer JA
影响因子：
3.7
作者：
Keitel, Verena;Ullmer, Christoph;Haeussinger, Dieter
通讯作者：
Haeussinger, Dieter
影响因子：
3.5
作者：
Hopp, Katharina;Heyer, Christina M.;Harris, Peter C.
通讯作者：
Harris, Peter C.
影响因子：
29.4
作者：
Gradilone SA;Masyuk TV;Huang BQ;Banales JM;Lehmann GL;Radtke BN;Stroope A;Masyuk AI;Splinter PL;LaRusso NF
通讯作者：
LaRusso NF
影响因子：
4
作者：
Doherty D;Parisi MA;Finn LS;Gunay-Aygun M;Al-Mateen M;Bates D;Clericuzio C;Demir H;Dorschner M;van Essen AJ;Gahl WA;Gentile M;Gorden NT;Hikida A;Knutzen D;Ozyurek H;Phelps I;Rosenthal P;Verloes A;Weigand H;Chance PF;Dobyns WB;Glass IA
通讯作者：
Glass IA