Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Zollner, G; Fickert, P; Zenz, R; Fuchsbichler, A; Stumptner, C; Kenner, L; Ferenci, P; Stauber, RE; Krejs, GJ; Denk, H; Zatloukal, K; Trauner, M.
Hepatobiliary transporter expression in percutaneous liver biopsies of patients with cholestatic liver diseases.
Hepatology. 2001; 33(3):633-646
Doi: 10.1053/jhep.2001.22646
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
Google Scholar
- Führende Autor*innen der Med Uni Graz
- Trauner Michael
- Zollner Gernot
- Co-Autor*innen der Med Uni Graz
- Denk Helmut
- Fickert Peter
- Kenner Lukas
- Krejs Günter Josef
- Stauber Rudolf
- Stumptner Cornelia
- Zatloukal Kurt
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Reduced hepatobiliary transporter expression could explain impaired hepatic uptake and excretion of bile salts and other biliary constituents resulting in cholestasis and jaundice. Because little is known about alterations of hepatobiliary transport systems in human cholestatic liver diseases, it was the aim of this study to investigate such potential changes. Hepatic mRNA levels in hepatobiliary transport systems for bile salts (NTCP, BSEP), organic anions (OATP2, MRP2, MRP3), organic cations (MDR1), phospholipids (MDR3), and aminophospholipids (FIC1) were determined in 37 human liver biopsies and control livers by competitive reverse-transcription polymerase chain reaction (RT-PCR). Transporter tissue distribution was investigated by immunofluorescence microscopy. In patients with inflammation-induced icteric cholestasis (mainly cholestatic alcoholic hepatitis), mRNA levels of NTCP, OATP2, and BSEP were reduced by 41% (P <.001), 49% (P <.005), and 34% (P <.05) compared with controls, respectively. In addition, NTCP and BSEP immunostaining was reduced. MRP2 mRNA levels remained unchanged, but canalicular immunolabeling for MRP2 was also decreased. mRNA expression of MRP3, MDR1, MDR3, and FIC1 remained unchanged. In contrast to the alterations of transporter expression in inflammation-induced icteric cholestasis, transporter expression did not change in anicteric cholestasis caused by primary biliary cirrhosis (PBC) stages I and II. In conclusion, reduced expression of hepatobiliary transport systems for bile salts and other organic anions may contribute to inflammation-induced cholestasis in humans. Reduction of transporter gene expression can occur at the mRNA level as observed for NTCP, OATP2, and BSEP. However, reduced MRP2 immunostaining in the presence of conserved MRP2 mRNA levels suggests an additional role for posttranscriptional/posttranslational mechanisms.
- Find related publications in this database (using NLM MeSH Indexing)
- ATP-Binding Cassette Transporters - metabolism
- Adenosine Triphosphatases - genetics
- Adult -
- Anions - metabolism
- Bile Acids and Salts - metabolism
- Bile Ducts - metabolism
- Biopsy -
- Carrier Proteins - genetics Carrier Proteins - metabolism
- Cholestasis - metabolism Cholestasis - pathology
- Female -
- Fluorescent Antibody Technique -
- Humans -
- Liver - metabolism Liver - pathology
- Male -
- Middle Aged -
- P-Glycoprotein - metabolism
- P-Glycoproteins - metabolism
- RNA, Messenger - metabolism
- Reference Values -