Wu Bo, Tian Xinbei, Wang Weipeng, Zhu Jing, Lu Ying, Du Jun, Xiao Yongtao
Department of Pediatric Surgery, Xin Hua Hospital School of Medicine, Shanghai Jiao Tong University Shanghai China.
Department of Pediatric Gastroenterology and Nutrition Shanghai Institute of Pediatric Research Shanghai China.
Pediatr Investig. 2022 Mar 22;6(2):100-110. doi: 10.1002/ped4.12317. eCollection 2022 Jun.
Cadherin-11 (CDH11), a cell-to-cell adhesion molecule, is implicated in the fibrotic process of several organs. Biliary atresia (BA) is a common cholestatic liver disease featuring cholestasis and progressive liver fibrosis in children. Cholestatic liver fibrosis may progress to liver cirrhosis and lacks effective therapeutic strategies. Currently, the role of CDH11 in cholestatic liver fibrosis remains unclear.
This study aimed to explore the functions of CDH11 in cholestatic liver fibrosis.
The expression of in BA livers was evaluated by database analysis and immunostaining. Seven BA liver samples were used for immunostaining. The wild type (Wt) and knockout ( ) mice were subjected to bile duct ligation (BDL) to induce cholestatic liver fibrosis. The serum biochemical analysis, liver histology, and western blotting were used to assess the extent of liver injury and fibrosis as well as activation of transforming growth factor-β (TGF-β)/Smad pathway. The effect of CDH11 on the activation of hepatic stellate cell line LX-2 cells was investigated.
Analysis of public RNA-seq datasets showed that expression levels were significantly increased in livers of BA, and CDH11 was correlated with liver fibrosis in BA. BDL-induced liver injury and liver fibrosis were attenuated in mice compared to Wt mice. The protein expression levels of phosphorylated Smad2/3 were decreased in livers of BDL mice compared to Wt BDL mice. knockdown inhibited the activation of LX-2 cells.
CDH11 plays an important role in cholestatic liver fibrosis and may represent a potential therapeutic target for cholestatic liver disease, such as BA.
钙黏蛋白-11（CDH11）是一种细胞间黏附分子，与多个器官的纤维化过程有关。胆道闭锁（BA）是一种常见的儿童胆汁淤积性肝病，其特征为胆汁淤积和进行性肝纤维化。胆汁淤积性肝纤维化可能进展为肝硬化，且缺乏有效的治疗策略。目前，CDH11在胆汁淤积性肝纤维化中的作用尚不清楚。
本研究旨在探讨CDH11在胆汁淤积性肝纤维化中的功能。
通过数据库分析和免疫染色评估BA肝脏中CDH11的表达。使用7个BA肝脏样本进行免疫染色。将野生型（Wt）和CDH11基因敲除（Cd11-/-）小鼠进行胆管结扎（BDL）以诱导胆汁淤积性肝纤维化。采用血清生化分析、肝脏组织学检查和蛋白质印迹法评估肝损伤和纤维化程度以及转化生长因子-β（TGF-β）/Smad信号通路的激活情况。研究CDH11对肝星状细胞系LX-2细胞激活的影响。
对公共RNA测序数据集的分析表明，BA肝脏中CDH11的表达水平显著升高，且CDH11与BA中的肝纤维化相关。与Wt小鼠相比，Cd11-/-小鼠中BDL诱导的肝损伤和肝纤维化有所减轻。与Wt BDL小鼠相比，Cd11-/- BDL小鼠肝脏中磷酸化Smad2/3的蛋白表达水平降低。CDH11基因敲低抑制了LX-2细胞的激活。
CDH11在胆汁淤积性肝纤维化中起重要作用，可能是胆汁淤积性肝病（如BA）的潜在治疗靶点。
