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Article: Downregulation of Hes1 expression in experimental biliary atresia and its effects on bile duct structure

TitleDownregulation of Hes1 expression in experimental biliary atresia and its effects on bile duct structure
Authors
KeywordsBiliary atresia
EpCAM
Epithelial cells 3D culture
Hes1
Rhesus rotavirus
Issue Date2018
PublisherBaishideng Publishing Group. The Journal's web site is located at http://www.wjgnet.com/1007-9327/index.htm
Citation
World Journal of Gastroenterology, 2018, v. 24 n. 29, p. 3260-3272 How to Cite?
AbstractAIM: To analyze the expression and function of the Notch signaling target gene Hes1 in a rhesus rotavirus-induced mouse biliary atresia model. METHODS: The morphologies of biliary epithelial cells in biliary atresia patients and in a mouse model were examined by immunohistochemical staining. Then, the differential expression of Notch signaling pathway-related molecules was investigated. Further, the effects of the siRNA-mediated inhibition of Hes1 expression were examined using a biliary epithelial cell 3D culture system. RESULTS: Both immature (EpCAM+) and mature (CK19+) biliary epithelial cells were detected in the livers of biliary atresia patients without a ductile structure and in the mouse model with a distorted bile duct structure. The hepatic expression of transcripts for most Notch signaling molecules were significantly reduced on day 7 but recovered to normal levels by day 14, except for the target molecule Hes1, which still exhibited lower mRNA and protein levels. Expression of the Hes1 transcriptional co-regulator, RBP-Jκ was also reduced. A 3D gel culture system promoted the maturation of immature biliary epithelial cells, with increased expression of CK19+ cells and the formation of a duct-like structure. The administration of Hes1 siRNA blocked this process. As a result, the cells remained in an immature state, and no duct-like structure was observed. CONCLUSION: Our data indicated that Hes1 might contribute to the maturation and the cellular structure organization of biliary epithelial cells, which provides new insight into understanding the pathology of biliary atresia.
Persistent Identifierhttp://hdl.handle.net/10722/269466
ISSN
2017 Impact Factor: 3.3
2015 SCImago Journal Rankings: 1.076
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhang, R-
dc.contributor.authorZeng, XH-
dc.contributor.authorLin, ZF-
dc.contributor.authorFu, M-
dc.contributor.authorTong, YL-
dc.contributor.authorLui, VCH-
dc.contributor.authorTam, PKH-
dc.contributor.authorLamb, JR-
dc.contributor.authorXia, HM-
dc.contributor.authorChen, Y-
dc.date.accessioned2019-04-24T08:08:16Z-
dc.date.available2019-04-24T08:08:16Z-
dc.date.issued2018-
dc.identifier.citationWorld Journal of Gastroenterology, 2018, v. 24 n. 29, p. 3260-3272-
dc.identifier.issn1007-9327-
dc.identifier.urihttp://hdl.handle.net/10722/269466-
dc.description.abstractAIM: To analyze the expression and function of the Notch signaling target gene Hes1 in a rhesus rotavirus-induced mouse biliary atresia model. METHODS: The morphologies of biliary epithelial cells in biliary atresia patients and in a mouse model were examined by immunohistochemical staining. Then, the differential expression of Notch signaling pathway-related molecules was investigated. Further, the effects of the siRNA-mediated inhibition of Hes1 expression were examined using a biliary epithelial cell 3D culture system. RESULTS: Both immature (EpCAM+) and mature (CK19+) biliary epithelial cells were detected in the livers of biliary atresia patients without a ductile structure and in the mouse model with a distorted bile duct structure. The hepatic expression of transcripts for most Notch signaling molecules were significantly reduced on day 7 but recovered to normal levels by day 14, except for the target molecule Hes1, which still exhibited lower mRNA and protein levels. Expression of the Hes1 transcriptional co-regulator, RBP-Jκ was also reduced. A 3D gel culture system promoted the maturation of immature biliary epithelial cells, with increased expression of CK19+ cells and the formation of a duct-like structure. The administration of Hes1 siRNA blocked this process. As a result, the cells remained in an immature state, and no duct-like structure was observed. CONCLUSION: Our data indicated that Hes1 might contribute to the maturation and the cellular structure organization of biliary epithelial cells, which provides new insight into understanding the pathology of biliary atresia.-
dc.languageeng-
dc.publisherBaishideng Publishing Group. The Journal's web site is located at http://www.wjgnet.com/1007-9327/index.htm-
dc.relation.ispartofWorld Journal of Gastroenterology-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectBiliary atresia-
dc.subjectEpCAM-
dc.subjectEpithelial cells 3D culture-
dc.subjectHes1-
dc.subjectRhesus rotavirus-
dc.titleDownregulation of Hes1 expression in experimental biliary atresia and its effects on bile duct structure-
dc.typeArticle-
dc.identifier.emailLui, VCH: vchlui@hku.hk-
dc.identifier.emailTam, PKH: paultam@hku.hk-
dc.identifier.emailChen, Y: ychenc@hku.hk-
dc.identifier.authorityLui, VCH=rp00363-
dc.identifier.authorityTam, PKH=rp00060-
dc.identifier.authorityChen, Y=rp01318-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.3748/wjg.v24.i29.3260-
dc.identifier.pmid30090006-
dc.identifier.pmcidPMC6079292-
dc.identifier.scopuseid_2-s2.0-85051204704-
dc.identifier.hkuros297317-
dc.identifier.volume24-
dc.identifier.issue29-
dc.identifier.spage3260-
dc.identifier.epage3272-
dc.identifier.isiWOS:000440779200006-
dc.publisher.placeUnited States-

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