Mechanism of NOTCH2 in promoting intrahepatic bile duct development

Abstract Background The Notch signaling pathway plays a crucial role in intrahepatic bile duct development. Here, we aimed to investigate the effect of the Notch receptor, NOTCH2, on intrahepatic bile duct development to better understand congenital intrahepatic bile duct dysplasia. Results Estradio...

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Main Authors: Chen Dong, Sheng-xuan Liu, Biao Zou, Sai-nan Shu, Ben-ping Zhang
Format: Article
Language:English
Published: BMC 2025-08-01
Series:BMC Gastroenterology
Subjects:
Online Access:https://doi.org/10.1186/s12876-025-04217-y
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author Chen Dong
Sheng-xuan Liu
Biao Zou
Sai-nan Shu
Ben-ping Zhang
author_facet Chen Dong
Sheng-xuan Liu
Biao Zou
Sai-nan Shu
Ben-ping Zhang
author_sort Chen Dong
collection DOAJ
description Abstract Background The Notch signaling pathway plays a crucial role in intrahepatic bile duct development. Here, we aimed to investigate the effect of the Notch receptor, NOTCH2, on intrahepatic bile duct development to better understand congenital intrahepatic bile duct dysplasia. Results Estradiol increased NOTCH2 and its downstream proteins expression, which promoted the differentiation of hepatoblasts into intrahepatic cholangiocytes and the development of intrahepatic bile ducts by upregulating the Notch signaling pathway. NOTCH2 siRNA inhibited the above processes (P < 0.05). There was no significant difference between estradiol and estradiol + non-targeting siRNA groups (P > 0.1). Conclusions In conclusion, the activation of the Notch signaling pathway leads to increased NOTCH2 expression, which promotes the differentiation of hepatoblasts into intrahepatic cholangiocytes and the development of intrahepatic bile ducts during embryonic stages in C57BL/6CrSlc mice. The results of this study may provide a theoretical basis for infantile intrahepatic cholestasis treatment.
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series BMC Gastroenterology
spelling doaj-art-33caf834cf354c16bb9ca52fef84bc992025-08-24T11:33:02ZengBMCBMC Gastroenterology1471-230X2025-08-012511910.1186/s12876-025-04217-yMechanism of NOTCH2 in promoting intrahepatic bile duct developmentChen Dong0Sheng-xuan Liu1Biao Zou2Sai-nan Shu3Ben-ping Zhang4Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Background The Notch signaling pathway plays a crucial role in intrahepatic bile duct development. Here, we aimed to investigate the effect of the Notch receptor, NOTCH2, on intrahepatic bile duct development to better understand congenital intrahepatic bile duct dysplasia. Results Estradiol increased NOTCH2 and its downstream proteins expression, which promoted the differentiation of hepatoblasts into intrahepatic cholangiocytes and the development of intrahepatic bile ducts by upregulating the Notch signaling pathway. NOTCH2 siRNA inhibited the above processes (P < 0.05). There was no significant difference between estradiol and estradiol + non-targeting siRNA groups (P > 0.1). Conclusions In conclusion, the activation of the Notch signaling pathway leads to increased NOTCH2 expression, which promotes the differentiation of hepatoblasts into intrahepatic cholangiocytes and the development of intrahepatic bile ducts during embryonic stages in C57BL/6CrSlc mice. The results of this study may provide a theoretical basis for infantile intrahepatic cholestasis treatment.https://doi.org/10.1186/s12876-025-04217-yNOTCH2Notch signaling pathwayHepatoblastIntrahepatic bile duct
spellingShingle Chen Dong
Sheng-xuan Liu
Biao Zou
Sai-nan Shu
Ben-ping Zhang
Mechanism of NOTCH2 in promoting intrahepatic bile duct development
BMC Gastroenterology
NOTCH2
Notch signaling pathway
Hepatoblast
Intrahepatic bile duct
title Mechanism of NOTCH2 in promoting intrahepatic bile duct development
title_full Mechanism of NOTCH2 in promoting intrahepatic bile duct development
title_fullStr Mechanism of NOTCH2 in promoting intrahepatic bile duct development
title_full_unstemmed Mechanism of NOTCH2 in promoting intrahepatic bile duct development
title_short Mechanism of NOTCH2 in promoting intrahepatic bile duct development
title_sort mechanism of notch2 in promoting intrahepatic bile duct development
topic NOTCH2
Notch signaling pathway
Hepatoblast
Intrahepatic bile duct
url https://doi.org/10.1186/s12876-025-04217-y
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