Expression level of vitamin D receptor in intrahepatic bile duct epithelial cells and its clinical significance in children with biliary atresia / 中华实用儿科临床杂志

ABSTRACT

Objective:To explore the possible role and clinical significance of vitamin D receptor (VDR) in intrahepatic bile duct epithelial cells (IBDECs) in biliary atresia (BA).Methods:A retrospective analysis was performed on expression level of VDR in IBDECs of 38 BA children who underwent Kasai surgery in the Second Affiliated Hospital of Xi′an Jiaotong University and the Children′s Hospital of Xi′an Jiaotong University from January 2015 to December 2019.Expression level of VDR in IBDECs of 38 children with BA was detected by immunohistochemical staining, and that in children with choledochal cysts was detected as negative control.Masson staining was performed to examine the degree of liver fibrosis.The correlation between the expression level of VDR in IBDECs of children with BA, and the degree of liver fibrosis during operation, the incidence of refractory cholangitis after Kasai portoenterostomy and the survival time of autologous liver was analyzed.Human intrahepatic bile duct epithelial cells (HiBECs) were induced with dsRNA virus infection by polyinosinic acid-polycytidylic acid [Poly(I∶C)] in vitro, followed by detection of cell activity, apoptosis and VDR level.The differences between 2 independent groups were analyzed using Student t test.The relationship between the expression of VDR and clinicopathologic characteristics was conducted with χ2 test or Fisher′ s test.The Kaplan- Meier survival curve was used to analyze the differences in the survival time of autologous liver after Kasai in BA children with different VDR expression levels. Results:A total of 38 children with BA were included in this study.Among them, 23 cases showed no significant decrease of VDR protein level in IBDECs, and 15 cases showed a significant decrease in IBDECs.Compared with BA children without a significant decrease in VDR level in IBDECs, much severer liver fibrosis ( P<0.001) and significantly higher incidence of refractory cholangitis after Kasai procedure ( P=0.017) were detected in those with a significant decrease in VDR level.Compared with the control group, BA children with significantly lower VDR expression levels in HiBECs had a shorter autologous liver survival time ( P=0.030). Poly (I∶C) increased the apoptotic rate of HiBECs ( P<0.000 1) and decreased cell activity of HiBECs ( P<0.05), which significantly stimulated the secretion of inflammatory factors (interferon, tumor necrosis factor-α, interleukin-6) in the culture medium of HiBECs ( P<0.001). Poly (I∶C) significantly decreased the expression level of VDR protein in HiBECs ( P<0.001). Conclusions:Poly (I∶C) causes HiBECs damage and decreases VDR expression level in HiBECs of BA children, and the significantly decreased VDR expression level in IBDECs may be a marker of poor prognosis of BA.