期刊论文详细信息
Frontiers in Pediatrics 卷:8
YAP Activation and Implications in Patients and a Mouse Model of Biliary Atresia
Rui Dong1  Chao Zheng1  Yifan Yang1  Shan Zheng1  Fa-Xing Yu2  Jiaqian Luo2 
[1] Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai, China;
[2] Institute of Pediatrics, Children's Hospital of Fudan University and Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China;
关键词: Biliary Atresia;    yes-associated protein;    hippo signaling pathway;    liver fibrosis;    Recombinant Ankyrin Repeat Domain Protein 1;   
DOI  :  10.3389/fped.2020.618226
来源: DOAJ
【 摘 要 】

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.

【 授权许可】

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