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

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

EBioMedicine (2018-08-15)
Yongtao Xiao, Weihui Yan, Ying Lu, Kejun Zhou, Wei Cai
ABSTRACT

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 < .001] 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 NTSR1and 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-SLC10A2 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
SR 48692, ≥98% (HPLC)