Developmental expression of canalicular transporter genes in human liver

J Hepatol. 2005 Sep;43(3):472-7. doi: 10.1016/j.jhep.2005.02.030.

Abstract

Background/aims: BSEP, MRP2, and MDR3 are major hepatic canalicular transporters mediating bile secretion. Their expression in human liver during development has not been reported.

Methods: Human liver samples from fetus at gestational age 14-20 weeks, adult livers and liver samples of infants with biliary atresia were tested for mRNA expression of BSEP, MDR3, MRP2, NTCP, FIC1, and FXR genes by using real-time RT-PCR. Immunohistochemical staining of BSEP, MDR3, and MRP2 were performed on fetal and adult livers.

Results: All the genes tested were expressed at mid-gestational age. MDR3 and NTCP showed significant lower levels in fetal livers compared to adults. In patients with biliary atresia, all the genes tested showed higher mean expression levels than adults except for NTCP, but not statistically significant. The immunohistochemical staining of MRP2 in fetal liver was canalicular, BSEP showed both intracellular and canalicular staining, and MDR3 staining was faint, only occasional canalicular pattern could be seen.

Conclusions: The major canalicular transporter genes are expressed at mid-gestational stage during human fetal development, but are different in expression level and targeting pattern, indicating differential regulation and maturation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • ATP-Binding Cassette Transporters / genetics
  • Adult
  • Female
  • Fetal Development
  • Gene Expression Regulation, Developmental*
  • Gestational Age
  • Humans
  • Liver / embryology
  • Liver / physiology*
  • Membrane Transport Proteins / genetics*
  • Multidrug Resistance-Associated Proteins / genetics*
  • Organic Anion Transporters, Sodium-Dependent / genetics
  • Pregnancy
  • Pregnancy Trimester, Second
  • Symporters / genetics

Substances

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP-Binding Cassette Transporters
  • Membrane Transport Proteins
  • Multidrug Resistance-Associated Proteins
  • Organic Anion Transporters, Sodium-Dependent
  • Symporters
  • sodium-bile acid cotransporter
  • multidrug resistance-associated protein 2
  • multidrug resistance protein 3