Upregulation of cadherin‐11 contributes to cholestatic liver fibrosis
ABSTRACT Importance 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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-06-01
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| Series: | Pediatric Investigation |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/ped4.12317 |
| _version_ | 1818250088321908736 |
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| author | Bo Wu Xinbei Tian Weipeng Wang Jing Zhu Ying Lu Jun Du Yongtao Xiao |
| author_facet | Bo Wu Xinbei Tian Weipeng Wang Jing Zhu Ying Lu Jun Du Yongtao Xiao |
| author_sort | Bo Wu |
| collection | DOAJ |
| description | ABSTRACT Importance 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. Objective This study aimed to explore the functions of CDH11 in cholestatic liver fibrosis. Methods The expression of CDH11 in BA livers was evaluated by database analysis and immunostaining. Seven BA liver samples were used for immunostaining. The wild type (Wt) and CDH11 knockout (CDH11–/–) 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. Results Analysis of public RNA‐seq datasets showed that CDH11 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 CDH11–/– mice compared to Wt mice. The protein expression levels of phosphorylated Smad2/3 were decreased in livers of CDH11–/– BDL mice compared to Wt BDL mice. CDH11 knockdown inhibited the activation of LX‐2 cells. Interpretation CDH11 plays an important role in cholestatic liver fibrosis and may represent a potential therapeutic target for cholestatic liver disease, such as BA. |
| first_indexed | 2024-12-12T15:46:50Z |
| format | Article |
| id | doaj.art-b684168c1c834c0aa820b85d3a5565c0 |
| institution | Directory Open Access Journal |
| issn | 2574-2272 |
| language | English |
| last_indexed | 2024-12-12T15:46:50Z |
| publishDate | 2022-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pediatric Investigation |
| spelling | doaj.art-b684168c1c834c0aa820b85d3a5565c02022-12-22T00:19:44ZengWileyPediatric Investigation2574-22722022-06-016210011010.1002/ped4.12317Upregulation of cadherin‐11 contributes to cholestatic liver fibrosisBo Wu0Xinbei Tian1Weipeng Wang2Jing Zhu3Ying Lu4Jun Du5Yongtao Xiao6Department of Pediatric Surgery, Xin Hua Hospital School of Medicine, Shanghai Jiao Tong University Shanghai ChinaDepartment of Pediatric Surgery, Xin Hua Hospital School of Medicine, Shanghai Jiao Tong University Shanghai ChinaDepartment of Pediatric Surgery, Xin Hua Hospital School of Medicine, Shanghai Jiao Tong University Shanghai ChinaDepartment of Pediatric Surgery, Xin Hua Hospital School of Medicine, Shanghai Jiao Tong University Shanghai ChinaDepartment of Pediatric Gastroenterology and Nutrition Shanghai Institute of Pediatric Research Shanghai ChinaDepartment of Pediatric Gastroenterology and Nutrition Shanghai Institute of Pediatric Research Shanghai ChinaDepartment of Pediatric Surgery, Xin Hua Hospital School of Medicine, Shanghai Jiao Tong University Shanghai ChinaABSTRACT Importance 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. Objective This study aimed to explore the functions of CDH11 in cholestatic liver fibrosis. Methods The expression of CDH11 in BA livers was evaluated by database analysis and immunostaining. Seven BA liver samples were used for immunostaining. The wild type (Wt) and CDH11 knockout (CDH11–/–) 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. Results Analysis of public RNA‐seq datasets showed that CDH11 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 CDH11–/– mice compared to Wt mice. The protein expression levels of phosphorylated Smad2/3 were decreased in livers of CDH11–/– BDL mice compared to Wt BDL mice. CDH11 knockdown inhibited the activation of LX‐2 cells. Interpretation CDH11 plays an important role in cholestatic liver fibrosis and may represent a potential therapeutic target for cholestatic liver disease, such as BA.https://doi.org/10.1002/ped4.12317Cadherin‐11Biliary atresiaCholestatic liver fibrosisTGF‐β/Smad |
| spellingShingle | Bo Wu Xinbei Tian Weipeng Wang Jing Zhu Ying Lu Jun Du Yongtao Xiao Upregulation of cadherin‐11 contributes to cholestatic liver fibrosis Pediatric Investigation Cadherin‐11 Biliary atresia Cholestatic liver fibrosis TGF‐β/Smad |
| title | Upregulation of cadherin‐11 contributes to cholestatic liver fibrosis |
| title_full | Upregulation of cadherin‐11 contributes to cholestatic liver fibrosis |
| title_fullStr | Upregulation of cadherin‐11 contributes to cholestatic liver fibrosis |
| title_full_unstemmed | Upregulation of cadherin‐11 contributes to cholestatic liver fibrosis |
| title_short | Upregulation of cadherin‐11 contributes to cholestatic liver fibrosis |
| title_sort | upregulation of cadherin 11 contributes to cholestatic liver fibrosis |
| topic | Cadherin‐11 Biliary atresia Cholestatic liver fibrosis TGF‐β/Smad |
| url | https://doi.org/10.1002/ped4.12317 |
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