Developmental expression of canalicular transporter genes in human liver

Huey-Ling Chen1, Hui-Ling Chen, Yu-Jung Liu

  • 1Department of Pediatrics, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 100, Taiwan, ROC.

Insights

Major hepatic transporters like BSEP, MRP2, and MDR3 are expressed in fetal liver by mid-gestation. Their expression levels and localization differ from adults, indicating developmental regulation.

Area of Science:

  • Hepatology
  • Developmental Biology
  • Molecular Biology

Background:

  • BSEP, MRP2, and MDR3 are key hepatic canalicular transporters essential for bile secretion.
  • Expression patterns of these transporters in human liver during development are largely unknown.

Purpose of the Study:

  • To investigate the expression of major hepatic canalicular transporters (BSEP, MRP2, MDR3) and related genes (NTCP, FIC1, FXR) in human fetal liver.
  • To compare their expression and localization with adult livers and in infants with biliary atresia.

Main Methods:

  • Real-time RT-PCR was used to quantify mRNA expression of BSEP, MDR3, MRP2, NTCP, FIC1, and FXR in fetal, adult, and biliary atresia liver samples.
  • Immunohistochemical staining was performed for BSEP, MDR3, and MRP2 on fetal and adult liver tissues.

Main Results:

  • All tested genes were expressed in mid-gestational fetal livers.
  • MDR3 and NTCP mRNA levels were significantly lower in fetal livers compared to adults.
  • Immunohistochemistry revealed canalicular MRP2, mixed intracellular/canalicular BSEP, and faint canalicular MDR3 staining in fetal livers.

Conclusions:

  • Key hepatic canalicular transporter genes are expressed during human fetal development.
  • Expression levels and cellular localization of these transporters undergo differential regulation and maturation during development.
Abstract

Related Concept Videos

Hepatic Drug Clearance: Role of Transporters01:14

Hepatic Drug Clearance: Role of Transporters

In the liver and bile canaliculi, influx and efflux transporters modification can influence intrinsic clearance. Transporters play a significant role in moving drugs within liver cells. Elaborate models, such as the Biopharmaceutical Classification System (BCS), are essential to relate transporters to drug disposition. This system categorizes drugs into four classes based on solubility and permeability, providing insights into elimination routes and the effects of transporters following oral...
Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters01:16

Pharmacogenetics of Drug Transporters: P-Glycoprotein and Solute Carrier Transporters

The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...
The Significance of Membrane Transport01:44

The Significance of Membrane Transport

The transport of solutes across the cell membrane is essential for metabolic processes, like maintaining cell size and volume, generating the action potential, exchanging nutrients and gases, etc. Membrane transport can be either passive or active. It can be simple diffusion, facilitated, or mediated transport aided by transport proteins such as transporters and channels.
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...
Liver Regeneration01:24

Liver Regeneration

The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are large...