Altered hepatobiliary gene expressions in PFIC1: ATP8B1 gene defect is associated with CFTR downregulation

@article{Demeilliers2006AlteredHG,
  title={Altered hepatobiliary gene expressions in PFIC1: ATP8B1 gene defect is associated with CFTR downregulation},
  author={Christine Demeilliers and Emmanuel Jacquemin and V{\'e}ronique Barbu and Martine Mergey and François Paye and Laura Fouassier and Nicolas Chignard and Chantal Housset and Nour-eddine Lomri},
  journal={Hepatology},
  year={2006},
  volume={43}
}
Recent reports in patients with PFIC1 have indicated that a gene defect in ATP8B1 could cause deregulations in bile salt transporters through decreased expression and/or activity of FXR. This study aimed to: (1) define ATP8B1 expression in human hepatobiliary cell types, and (2) determine whether ATP8B1 defect affects gene expressions related to bile secretion in these cells. ATP8B1 expression was detected by RT‐PCR in hepatocytes and cholangiocytes isolated from normal human liver and… 
ATP8B1 deficiency disrupts the bile canalicular membrane bilayer structure in hepatocytes, but FXR expression and activity are maintained.
TLDR
ATP8B1 deficiency predisposes to cholestasis by favoring bile acid-induced injury in the canalicular membrane but does not directly affect FXR expression, which may occur in PFIC1 as a secondary phenomenon associated with cholESTasis.
ATP8B1 Gene Expression Is Driven by a Housekeeping-Like Promoter Independent of Bile Acids and Farnesoid X Receptor
TLDR
The structure of the ATP8B1 gene is complex and the previously published transcription start site is not significant, and in vitro analysis demonstrated that the main promoter drives constitutive ATP8 B1 gene expression independent of bile acids.
Intestinal bile salt absorption in Atp8b1 deficient mice.
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TLDR
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Constitutive Androstane Receptor contributes towards increased drug clearance in cholestasis
TLDR
High-throughput RNA sequencing on various liver injury models revealed robust induction of drug metabolizing genes in cholestatic livers, specific to genes regulated by nuclear receptor CAR (Constitutive Androstane Receptor), which can alter therapeutic efficacy of certain drugs in a subset of cholESTatic individuals.
Regulation of hepatic ABCC transporters by xenobiotics and in disease states
TLDR
The regulation of hepatic ABCC transporters in humans and rodents by a variety of xenobiotics, under disease states and in genetically modified animal models deficient in transcription factors, transporter, and cell-signaling molecules is described.
Progressive familial intrahepatic cholestasis
TLDR
Diagnosis is based on clinical manifestations, liver ultrasonography, cholangiography and liver histology, as well as on specific tests for excluding other causes of childhood cholestasis, and most PFIC patients are ultimately candidates for liver transplantation.
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TLDR
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