Inositol-requiring enzyme 1α/X-box protein 1 pathway expression is impaired in pediatric cholestatic liver disease explants.

ABSTRACT:

Background

Increased intrahepatic bile acids cause endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) is activated to maintain homeostasis. UPR dysregulation, including the inositol-requiring enzyme 1α/X-box protein 1 (IRE1α/XBP1) pathway, is associated with adult liver diseases but has not been characterized in pediatric liver diseases. We evaluated hepatic UPR expression in pediatric cholestatic liver disease (CLD) explants and hypothesize that an inability to appropriately activate the hepatic IRE1α/XBP1 pathway is associated with the pathogenesis of CLD.

Methods

We evaluated 34 human liver explants, including: pediatric CLD (Alagille, ALGS, and progressive familial intrahepatic cholestasis, PFIC), pediatric non-cholestatic liver disease controls (a

SUBMITTER: Kriegermeier A 

PROVIDER: S-EPMC9754178 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature