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Oestradiol promotes the intrahepatic bile duct development of C57BL/6CrSlc mice during embryonic period via Notch signalling pathway |
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| Authors: | Chen Dong Ben-ping Zhang Yan-Qin Ying Ling Hou Wei Wu Hong Wei Xiao-ping Luo |
| Affiliation: | 1. Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;2. Department of Endocrinology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China Contribution: Data curation (lead), Investigation (equal), Writing - review & editing (supporting);3. Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China Contribution: Methodology (equal), Writing - review & editing (equal);4. Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China Contribution: Data curation (equal), Writing - review & editing (equal);5. Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China Contribution: Investigation (supporting), Writing - review & editing (supporting) |
| Abstract: | Oestradiol (E2) is a critical factor for multiple systems' development during the embryonic period. Here, we aimed to investigate the effects of oestradiol on intrahepatic bile duct development, which may allow a better understanding of congenital bile duct dysplasia. DLK+ hepatoblasts were extracted from the C57BL/6CrSlc foetal mice and randomly divided into control group, oestradiol groups (1, 10, 100 nM) and oestradiol (10 nM) + DAPT (inhibitor of Notch signalling; 40 µM) group for in vitro experiments. For in vivo analysis, pregnant mice were divided into control group, oestradiol (intraperitoneal injection of 0.6 mg/kg/day) ± DAPT (subcutaneous injection of 10 mg/kg/day) groups and tamoxifen (gavage administration of 0.4 mg/kg/day) group. The results showed that oestradiol promoted hepatoblast differentiation into cholangiocytes and intrahepatic bile duct development during the embryonic period. Tamoxifen, an antioestrogenic drug, inhibited the above processes. Moreover, oestradiol promoted the expression of Notch signalling pathway-associated proteins and genes both in vitro and in vivo. Notably, DAPT addition inhibited the oestradiol-mediated effects. In conclusion, oestradiol can promote hepatoblast differentiation into cholangiocytes and intrahepatic bile duct development of C57BL/6CrSlc mice during embryonic period via the Notch signalling pathway. |
| Keywords: | bile duct cholangiocyte hepatoblast Notch signalling pathway oestradiol |