Compared to controls, basolateral uptake systems (NTCP, OATP2) were reduced, canalicular export pumps for bile salts and bilirubin (BSEP, MRP2) were preserved, while canalicular MDR P-glycoproteins (MDR1, MDR3) and the basolateral efflux pump MRP3 were increased in PBC.
Double immunofluorescence labeling with a canalicular marker (dipeptidyl peptidase IV) demonstrated proper canalicular localization of BSEP and MRP2 in PBC.
Although an impact of rare variants on BSEP and MDR3 function cannot beruled out, our data do not support a strong role of BSEP and MDR3 genetic variations in the pathogenesis of PBC and PSC.
These results suggested that BSEPrs473351 was closely associated with the susceptibility of PBC and if people with BSEPrs2287618 were diagnosed as PBC, the UDCA treatment was not satisfactory.
We found no evidence for deficient or severely reduced intrahepatic MDR3 mRNA in primary biliary cirrhosis, nor were mRNA levels altered significantly by virus-induced inflammation or by cirrhosis.
Compared to controls, basolateral uptake systems (NTCP, OATP2) were reduced, canalicular export pumps for bile salts and bilirubin (BSEP, MRP2) were preserved, while canalicular MDR P-glycoproteins (MDR1, MDR3) and the basolateral efflux pump MRP3 were increased in PBC.
Indeed, MDR3 variants could play a role as modifier gene in primary biliary cirrhosis and primary sclerosing cholangitis, but their exact role needs further clarification.
The Hap 2/Hap 2 diplotype in MDR3 could therefore be potentially applied to DNA-based diagnosis in Japanese patients with PBC as a strong genetic biomarker for predicting the progression and prognosis of PBC.
The hepatic expression of multidrug-resistance protein 2 and multidrug-resistance protein 3 messenger RNAs was significantly elevated only in early-stage PBC patients.
Mutation screening of ABCB4 was carried out in 90 patients with idiopathic chronic cholestasis (ICC), primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), ICP, and JC.
The levels of expression of genes associated with choline uptake (OCT1 and CTL1), phosphatidylcholine synthesis (PEMT and BHMT), and phosphatidylcholine transport (MDR3) were significantly upregulated in PBC compared with control livers.
Although an impact of rare variants on BSEP and MDR3 function cannot beruled out, our data do not support a strong role of BSEP and MDR3 genetic variations in the pathogenesis of PBC and PSC.
This study aimed to determine the expression of hepatobiliary transport systems for bile salts (Na(+)/taurocholate cotransporter, NTCP; bile salt export pump, BSEP), organic anions (organic anion transporting protein, OATP2; canalicular conjugate export pump, MRP2; basolateral MRP homologue, MRP3), organic cations (canalicular multidrug export pump, MDR1), and phospholipids (canalicular phospholipid flippase MDR3) in livers from patients with advanced stages of PBC.
Double immunofluorescence labeling with a canalicular marker (dipeptidyl peptidase IV) demonstrated proper canalicular localization of BSEP and MRP2 in PBC.
We investigated the uptake transporters OATP2 (SLC21A6), OATP8 (SLC21A8), and NTCP (SLC10A1), the export pumps MRP2 (ABCC2), MRP3 (ABCC3), MRP6 (ABCC6), and P-glycoproteins (ABCB1, ABCB4, ABCB11), and radixin, in non-icteric primary biliary cirrhosis (PBC stages I-III) and control human liver needle-biopsies using immunofluorescence microscopy and semi-quantitative RT-PCR.
We investigated the uptake transporters OATP2 (SLC21A6), OATP8 (SLC21A8), and NTCP (SLC10A1), the export pumps MRP2 (ABCC2), MRP3 (ABCC3), MRP6 (ABCC6), and P-glycoproteins (ABCB1, ABCB4, ABCB11), and radixin, in non-icteric primary biliary cirrhosis (PBC stages I-III) and control human liver needle-biopsies using immunofluorescence microscopy and semi-quantitative RT-PCR.