The Role Of Notch Signaling Pathway In The Progression Of Liver Fibrosis In Biliary Atresia

Objective To investigate the role of Notch signaling pathway in the progression of biliary atresia in liver fibrosis.Methods According to Ohkuma’s liver fibrosis grading standard,40 children with biliary atresia were divided into 4 subgroups;children with congenital biliary dilatation 5 cases;5 cases of normal liver tissue samples.The expression levels of Notch pathway elements(including Notch-1 receptor,Jagged-1 ligand and Hes-1target gene)in liver tissues were detected by immunohistochemistry.Results(1)Immunohistochemical qualitative results:Notch-1 was strongly expressed in BA group,positive expression in CBD group,weak expression in control group;Jagged-1 treatment was positive in BA group,weak expression in CBD group and control group;Hes-1 gene was positively expressed in BA group and CBD group,control group weak positive expression.(2)Immunohistochemical semi-quantitative results: Notch-1,Jagged-1,Hes-1 expression between the biliary atresia group and the control group were(0.174±0.037 vs.0.054±0.004,P<0.001),(0.182±0.055 vs.0.048±0.010,P,respectively)<0.001),(0.148±0.050 vs 0.050±0.023,P<0.001),the expression in liver tissue of children with biliary atresia was higher than that in the control group,and the difference was statistically significant.The expression of Notch-1,Jagged-1 and Hes-1 between the biliary atresia group and the CBD group were(0.174±0.037 vs.0.191±0.318,P>0.05),(0.182±0.055 vs.0.260±0.061,P>0.05).(0.148±0.050 vs.0.108±0.018,P<0.05),there was no significant difference between Notch-1 and Jagged-1 in the two groups.The difference between Hes-1 group was statistically significant.In the subgroup of biliary atresia,the expression level of Notch pathway elements increased with the degree of fibrosis(Notch-1: F=31.215,P<0.001;Jagged-1: F=13.914,P<0.001;Hes-1=66.127,P<0.001).Conclusion The abnormal activation of Notch signaling pathway elements in liver tissues of children with BA,which leads to changes in expression of Notch-1,Jagged-1,and Hes-1 are associated with the progression of biliary atresia liver fibrosis.The mechanism of the differential expression of Notch-1 betweenhepatocytes and HSCs on the progression of liver fibrosis needs to be further explored,and the over expression of Jagged-1 / Hes-1 leads to a series of physical and chemical changes in the liver,which may be one of the reasons for the rapid progress of liver fibrosis in children with BA.For children with BA,liver fibrosis keep progressing from the discovery of biliary atresia,Kasai procedure even to liver transplantation.If the liver fibrosis can be slowed,blocked,or even reversed,the prognosis of BA and the prevention of liver cirrhosis and liver failure can be greatly improved.From the results of this study,the Notch signaling pathway can be used as a potential therapeutic target to control the development of liver fibrosis in order to extend the survival time of native liver.