Related Experiment Video
Updated: Nov 18, 2025
A Mouse Model of Chronic Liver Fibrosis for the Study of Biliary Atresia
Published on: February 3, 2023
YAP Activation and Implications in Patients and a Mouse Model of Biliary Atresia
Chao Zheng1, Jiaqian Luo2, Yifan Yang1
1Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai, China.
Insights
Yes-associated protein (YAP) is elevated in biliary atresia (BA) livers, correlating with fibrosis. YAP and its target gene ANKRD1 may indicate BA progression and involve the Hippo signaling pathway in disease development.
Area of Science:
- Pediatric Hepatology
- Molecular Biology
- Signaling Pathways
Background:
- Biliary atresia (BA) is an infant liver disease causing fibrosis and requiring transplantation.
- The Hippo signaling pathway effector, Yes-associated protein (YAP), is crucial for bile ductal cell identity.
Purpose of the Study:
- To evaluate YAP and its target gene expression in BA.
- To investigate the role of YAP in BA-associated liver fibrosis and bile duct hyperplasia.
Main Methods:
- Analysis of liver tissues from 200 BA patients and 30 controls.
- Utilized RNA-seq, qPCR, immunohistochemistry, and immunoblotting.
- Assessed fibrosis using Masson's trichrome staining and the BARC system in human samples and a rhesus rotavirus (RRV)-induced mouse model.
Main Results:
- YAP expression is elevated in BA livers and positively correlates with fibrosis.
- The YAP target gene, ANKRD1, is also highly expressed in BA livers.
- YAP and ANKRD1 are significantly upregulated in an RRV-induced BA mouse model.
Conclusions:
- YAP expression correlates with bile duct hyperplasia and liver fibrosis in BA.
- YAP may serve as a biomarker for BA progression and liver fibrosis.
- The Hippo signaling pathway and YAP-induced ANKRD1 expression are implicated in BA pathogenesis.
Abstract:
Background and Aim: Biliary atresia (BA), an inflammatory destruction of the bile ducts, leads to liver fibrosis in infants and accounts for half of cases undergoing pediatric liver transplantation. Yes-associated protein (YAP), an effector of the Hippo signaling pathway, is critical in maintaining identities of bile ductal cells. Here, we evaluated the expression of YAP and YAP target genes in BA livers and a rhesus rotavirus (RRV)-induced BA mice model. Methods: Liver specimens collected from 200 BA patients were compared with those of 30 non-BA patients. Model mice liver tissues were also collected. The expression of YAP and YAP target genes were measured by transfection, RNA-seq, immunohistochemistry, immunoblot, and quantitative PCR. Masson's trichrome staining and the Biliary Atresia Research Consortium (BARC) system were utilized to score liver fibrosis status. Results: The expression of YAP is elevated and positively correlated with fibrosis in BA livers. Moreover, ANKRD1, which is identified as the target gene of YAP, is also highly expressed in BA livers. Consistent with clinical data, YAP and ANKRD1 are significantly upregulated in RRV-induced BA mouse model. Conclusions: YAP expression is closely correlated with the bile duct hyperplasia and liver fibrosis, and may serve as an indicator for liver fibrosis and BA progression. This study indicates an involvement of the Hippo signaling pathway in the development of BA, and the YAP induced ANKRD1 expression may also be related to bile duct hyperplasia in BA. This provides a new direction for more in-depth exploration of the etiology and pathogenesis of biliary atresia.
