title: Endoplasmic Reticulum Stress Is Implicated in Intestinal Failure-Associated Liver Disease.
abstract: BACKGROUND
  Intestinal failure-associated liver disease (IFALD) is the most serious consequence of long-term parenteral nutrition for intestinal failure. Little is known about the pathogenesis of IFALD, although many of the risk factors are also linked to endoplasmic reticulum stress (ERS). We propose that ERS may have a role in the development of IFALD.
  
  
  METHODS
  Archived liver tissue from patients with early and late IFALD, as well as from normal controls, was used for RNA extraction and immunohistochemistry to demonstrate the presence of ERS markers.
  
  
  RESULTS
  Mean relative RNA levels of glucose regulatory protein 78 in normal liver (n = 3), early IFALD (n = 15), and late IFALD (n = 5) were 0.5, 37.86, and 212.11, respectively. Mean relative expression of ERDj4 (ER DnaJ homologue 4, a downstream ERS effector) in normal liver, early IFALD, and late IFALD was 5.51, 216.68, and 213.22, respectively. The degree of splicing of X-box binding protein 1 in IFALD compared with normal liver was significantly higher (mean, 0.0779 normal, 0.102 early IFALD, 0.2063 late IFALD).
  
  
  CONCLUSIONS
  This is the first description of ERS in IFALD. This information may open up new therapeutic possibilities in the form of chemical chaperones known to ameliorate ERS.
authors: Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK lisa.sharkey@addenbrookes.nhs.uk.
authors: Lisa M
authors: LM
authors: Sharkey
authors: Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
authors: Susan E
authors: SE
authors: Davies
authors: Division of Gastroenterology and Hepatology, Department of Medicine, University of Cambridge, UK.
authors: Arthur
authors: A
authors: Kaser
authors: Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
authors: Jeremy M
authors: JM
authors: Woodward
mesh_terms: D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D059865:Endoplasmic Reticulum Stress; D050956:HSP40 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007410:Intestinal Diseases / Q000097:blood / Q000150:complications*; D008107:Liver Diseases / Q000097:blood / Q000150:complications*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D010288:Parenteral Nutrition / Q000009:adverse effects; D012326:RNA Splicing; D012307:Risk Factors; D000071717:X-Box Binding Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; C478021:DNAJB9 protein, human; D050956:HSP40 Heat-Shock Proteins; D008565:Membrane Proteins; D018832:Molecular Chaperones; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human
keywords: endoplasmic reticulum stress; intestinal failure; intestinal failure–associated liver disease; parenteral nutrition–associated liver disease