Impaired Bile Secretion Promotes Hepatobiliary Injury in Sickle Cell Disease.

ABSTRACT:

Background and aims

Hepatic crisis is an emergent complication affecting patients with sickle cell disease (SCD); however, the molecular mechanism of sickle cell hepatobiliary injury remains poorly understood. Using the knock-in humanized mouse model of SCD and SCD patient blood, we sought to mechanistically characterize SCD-associated hepato-pathophysiology applying our recently developed quantitative liver intravital imaging, RNA sequence analysis, and biochemical approaches.

Approach and results

SCD mice manifested sinusoidal ischemia, progressive hepatomegaly, liver injury, hyperbilirubinemia, and increased ductular reaction under basal conditions. Nuclear factor kappa B (NF-κB) activation in the liver of SCD mice inhibited farnesoid X receptor (FXR) signaling and its do

SUBMITTER: Vats R 

PROVIDER: S-EPMC7923682 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature