Neurotensin contributes to pediatric intestinal failure-associated liver disease via regulating intestinal bile acids uptake

作者：Xiao, Yongtao; Yan, Weihui; Lu, Ying; Zhou, Kejun; Cai, Wei^*

来源：EBioMedicine, 2018, 35: 133-141.

DOI：10.1016/j.ebiom.2018.08.006

• Intestinal failure
• Liver diseases
• Neurotensin
• Cholestasis
• ASBT

Although the pathogenesis of intestinal failure (IF)-associated liver disease (IFALD) is uncertain, IF-associated cholestasis mediated by the combination of intestinal injury and parenteral nutrition (PN) can lead to disturbed hepatocyte bile acids (BA) homeostasis and cause liver damages. We here show that neurotensin (NT: also known as NTS) concentrations were lower compared to healthy matched controls. Patients with cholestasis [56.1 ng/L (9.7-154.7) vs. 210.4 ng/L (134-400.4), p <.0011 had lower serum NT concentrations than others. In patients' ileum, the levels of NT mRNA were positively correlated with the apical sodium dependent bile acid transporter (ASBT) mRNA levels. In mice and in cultured intestinal cells, NT treatments stimulated the expression of ASBT and led to increase BA uptake via NT receptors (NTR1 and NTR3; also known as NTSR1 and NTSR3). In conclusion, these findings directly link NT with BA homeostasis, which provide an insight into the complex mechanisms mediating the development of liver disease in pediatric patients with IF.

• 出版日期2018-9
• 单位上海交通大学