Notch‐Hes1 signaling activation in Caroli disease and polycystic liver disease
Notch‐Hes1 signaling activation in Caroli disease and polycystic liver disease
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卡罗利病和多囊肝病中的 Notch-Hes1 信号激活
DOI：
10.1111/pin.13130
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发表时间：
2021
影响因子：
2.2
通讯作者：
Harada Kenichi
中科院分区：
文献类型：
--
作者：
Takahashi Kenta;Sato Yasunori;Yamamura Minako;Nakada Satoko;Tamano Yuko;Sasaki Motoko;Harada Kenichi
Notch信号通路在胆道树的形态发生中起着关键作用，但其在胆囊胆道疾病（如Caroli病（CD）和多囊性肝病（PLD））中的作用尚未确定。采用CD和PLD肝切片进行免疫染色，并与先天性肝纤维化（CHF）和von Meyenburg复合体（VMC）的结果进行比较。Notch受体1 （Notch receptor 1, Notch1）在所有CD和PLD患者的胆道上皮细胞核中的表达均升高，而在CHF和VMC患者中则维持在较低水平。此外，Notch2和Notch3在PLD胆道上皮细胞的细胞核中较好地表达。由此可见，Notch效应因子Hes1在CD和PLD的胆道上皮细胞中高表达，细胞增殖活性明显高于CD和PLD。Notch配体Delta - like 1在CD和PLD胆道上皮细胞中的表达显著增加，这可能与Notch1和Hes1的核过表达有关。这些结果表明Notch‐Hes1信号通路的异常激活可能是导致CD和PLD胆道胆囊形成进展的原因。
The Notch signaling pathway plays a key role in the morphogenesis of the biliary tree, but its involvement in cystic biliary diseases, such as Caroli disease (CD) and polycystic liver disease (PLD), has yet to be determined. Immunostaining was performed using liver sections of CD and PLD, and the results were compared with those of congenital hepatic fibrosis (CHF) and von Meyenburg complex (VMC). The expression of Notch receptor 1 (Notch1) was increased in the nuclei of biliary epithelial cells in all cases of CD and PLD, whereas it remained at a low level in CHF and VMC. In addition, Notch2 and Notch3 were preferably expressed in the nuclei of biliary epithelial cells of PLD. Accordingly, the Notch effector Hes1 was highly expressed in biliary epithelial cells of CD and PLD, and the cell proliferative activity was significantly higher in CD and PLD. The expression of the Notch ligand Delta‐like 1 was significantly increased in biliary epithelial cells of CD and PLD, which may be causally associated with the nuclear overexpression of Notch1 and Hes1. These results indicate that aberrant activation of the Notch‐Hes1 signaling pathway may be responsible for the progression of biliary cystogenesis in CD and PLD.