Induction of short heterodimer partner 1 precedes downregulation of Ntcp in bile duct-ligated mice

• DOI: 10.1152/ajpgi.00215.2001
• Publication Date: 2015-03-03T23:01:23Z
• Authors: Gernot Zollner; Peter Fickert; Dagmar Silbert; Andrea Fuchsbichler; Conny Stumptner; Kurt Zatloukal; Helmut Denk; Michael Trauner
• Keywords: Small heterodimer partner

Cholestasis is associated with retention of bile acids and reduced expression the Na + /taurocholate cotransporter (Ntcp), major hepatocellular acid uptake system. This study aimed to determine whether downregulation Ntcp in obstructive cholestasis 1) a consequence 2) mediated by induction transcriptional repressor short heterodimer partner 1 (SHP-1). To time course for changes serum levels as well SHP-1 steady-state mRNA levels, mice were subjected common duct ligation (CBDL) 3, 6, 12, 24, 72, 168 h compared sham-operated controls. Serum determined radioimmunoassay. assessed Northern blotting. In addition, protein was studied Western blotting immunofluorescence microscopy. Increased paralleled elevations followed CBDL mice. Maximal reached plateau phase after 6-h (12-fold; P < 0.001) preceded nadir (12%, 6 h. conclusion, acid-induced may, at least part, mediate These findings support concept that limits intracytoplasmatic accumulation potentially toxic acids.