Published online Aug 7, 2018. doi: 10.3748/wjg.v24.i29.3260
Peer-review started: April 23, 2018
First decision: May 9, 2018
Revised: June 3, 2018
Accepted: June 25, 2018
Article in press: June 25, 2018
Published online: August 7, 2018
An increased number of immature biliary epithelial cells and distorted bile ductules were observed in biliary atresia (BA), but the causes of these changes are unknown. The Notch signaling pathway is related to the development and differentiation of biliary epithelial cells. The target gene Hes1 is essential for tubular formation and maintenance. However, the effect of altered Hes1 expression in biliary atresia has not been established.
Notch signaling is one of the main pathways involved in bile duct development. However, its function in BA is not well known. Analysis of Notch signaling molecules using an established BA animal model, and 3D cell culture system might provide novel insights into the pathogenesis of BA.
The expression of Notch signaling pathway-related molecules was detected in a BA mouse model. The function of Hes1 downregulation was further examined using a 3D cell culture system. The results of this study can be expanded upon in future research of human BA patients by examining Hes1 expression and its relationship with BA pathogenesis.
Immature biliary epithelial cells and bile duct structure distortion were examined in BA patients and in a BA mouse model. The expression of Notch signaling pathway-related molecules was detected in the mouse model by qPCR, and the expression of Hes1 and its gene regulatory protein was further confirmed by Western blotting. Finally, in 3D cell culture, the effects of Hes1 inhibition induced by siRNA transfection on duct-like structure formation were observed.
The results revealed the presence of immature biliary epithelial cells and distorted structures in both the BA patients and animal model. The downregulation of Hes1 expression, together with its transcriptional co-regulator RBP-Jκ, was observed in the BA mouse model. The siRNA-mediated inhibition of Hes1 completely blocked duct-like structure formation in the 3D cell culture system. However, Hes1 expression in BA patients must be further evaluated to confirm its function in the disease process.
In conclusion, the results of the current study indicate that the immature biliary epithelial cells and defective duct-like structure formation in BA might be partly related to downregulation of the expression of the Notch signaling target gene Hes1. The use of a 3D epithelial cell culture system might help to identify other potential molecules, including those involved in epithelial cell maturation and duct-like structure formation.
The potential effects of Hes1 observed in the BA mouse model and cell culture involving biliary epithelial cell maturation and duct-like structure formation suggest that Hes1 might contribute to the pathogenesis of BA. However, further examination of BA patient samples is necessary to better understand the role of Hes1 in the BA disease process.