Xiao Yongtao, Zhou Ying, Chen Yingwei, Zhou Kejun, Wen Jie, Wang Yang, Wang Jun, Cai Wei
1] Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China [2] Shanghai Institute of Pediatric Research, Shanghai, China [3] Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China.
1] Department of Pediatric Surgery, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China [2] Shanghai Key Laboratory of Pediatric Gastroenterology and Nutrition, Shanghai, China.
Pediatr Res. 2015 Feb;77(2):310-5. doi: 10.1038/pr.2014.181. Epub 2014 Nov 19.
The epithelial-mesenchymal transition (EMT) has been implicated as a key mechanism in the pathogenesis of liver fibrosis. The miR-200 family has been shown to inhibit EMT.
Liver fibrosis levels were assessed with Masson's trichrome staining of liver samples obtained from biliary atresia (BA) patients. The expressions of cytokeratin-7 (CK-7) and α-smooth muscle actin (α-SMA) in the liver sections were detected by immunohistochemical and immunofluorescent staining. EMTs were induced by transforming growth factor (TGF)-β1 in human biliary epithelial cells (BECs) in vitro.
We showed that the EMT-related proteins CK-7 and α-SMA colocalized to the intrahepatic BECs in the liver sections of patients with BA. The level of α-SMA expression was related to liver fibrosis stage in BA. EMT in primary human intrahepatic BECs was induced by TGF-β1 in vitro. miR-200b is one member of the miR-200 family and significantly inhibited TGF-β1-mediated EMT in BECs.
Together, these data suggest that the occurrence of EMT in BECs might contribute to BA fibrosis. miR-200b significantly affects the development and progression of TGF-β1-dependent EMT and fibrosis in vitro.
上皮-间质转化（EMT）被认为是肝纤维化发病机制中的关键机制。已表明miR-200家族可抑制EMT。
采用Masson三色染色法评估从胆道闭锁（BA）患者获取的肝脏样本的肝纤维化水平。通过免疫组织化学和免疫荧光染色检测肝切片中细胞角蛋白-7（CK-7）和α-平滑肌肌动蛋白（α-SMA）的表达。体外用人胆管上皮细胞（BECs）经转化生长因子（TGF）-β1诱导EMT。
我们发现，在BA患者肝切片中，EMT相关蛋白CK-7和α-SMA共定位于肝内BECs。α-SMA表达水平与BA患者的肝纤维化分期相关。体外TGF-β1可诱导原代人肝内BECs发生EMT。miR-200b是miR-200家族的成员之一，可显著抑制BECs中TGF-β1介导的EMT。
总之，这些数据表明BECs中EMT的发生可能导致BA纤维化。miR-200b在体外显著影响TGF-β1依赖性EMT和纤维化的发生发展。
