Related Experiment Video
Updated: Jul 12, 2026
Mapping Hepatic Stellate Cell Morphology in Mouse Models of Liver Fibrosis
Published on: February 13, 2026
Disturbed colocalization of multidrug resistance protein 2 and radixin in human cholestatic liver diseases
Hideyuki Kojima1, Shinya Sakurai, Masahito Uemura
1Third Department of Internal Medicine, Nara Medical University, Kashihara, Japan. kojima@nmu-gw.naramed-u.ac.jp
Background And Aim:
Endocytic retrieval of multidrug resistance protein 2 (MRP2) is closely associated with cholestasis and may be attributed to the disturbed linking of MRP2 and radixin, a cross-linker between actin filaments and membrane proteins. This study aimed to investigate the role of radixin in the altered localization of MRP2 in various human cholestatic liver diseases.
Methods:
Using immunofluorescence microscopy, we investigated the localization and expression of MRP2 and radixin in various cholestatic liver diseases, such as drug-induced liver injury, obstructive jaundice, primary sclerosing cholangitis and autoimmune hepatitis. Changes in localization and expression were analyzed using Scion Image (software).
Results:
In the icteric drug-induced liver injury, MRP2 was localized outside as well as inside of ZO-1 staining, indicating endocytic retrieval from the canalicular membrane into the pericanalicular compartments of the hepatocytes. The colocalization of MRP2 and radixin observed in the controls was disturbed, and MRP2 fluorescence disappeared in the canaliculi with disrupted radixin staining. Disturbed colocalization of MRP2 and radixin as well as endocytic retrieval of MRP2 was found in the poorly drained obstructive jaundice. When drainage was good, MRP2 was exclusively colocalized with radixin. Similar findings were observed in autoimmune hepatitis and primary sclerosing cholangitis. In the controls, the immunostaining intensity curves for MRP2 and radixin were steeply elevated in the canaliculi. The intensity curves for MRP2 and radixin were broadened in the icteric drug-induced liver injury and poorly drained obstructive jaundice, indicating endocytic retrieval into the hepatocytes. The peak fluorescence intensities for MRP2 and radixin decreased in the icteric liver.
Conclusion:
Disturbed colocalization of MRP2 and radixin was common in various cholestatic liver diseases, which may be associated with endocytic retrieval of MRP2 due to failure in anchoring MRP2 in the canalicular membrane.
Insights
Radixin
Area of Science:
- Hepatology
- Cell Biology
- Molecular Medicine
Background:
- Cholestasis involves endocytic retrieval of multidrug resistance protein 2 (MRP2).
- This retrieval may stem from impaired linking between MRP2 and radixin, a protein connecting actin filaments to membrane proteins.
Purpose of the Study:
- To investigate radixin's role in the altered localization of MRP2 in human cholestatic liver diseases.
Main Methods:
- Immunofluorescence microscopy was used to examine MRP2 and radixin localization and expression in cholestatic liver diseases.
- Scion Image software analyzed changes in localization and expression.
Main Results:
- Disturbed colocalization of MRP2 and radixin was observed in various cholestatic conditions, including drug-induced liver injury and obstructive jaundice.
- Endocytic retrieval of MRP2 from the canalicular membrane into hepatocytes correlated with disrupted radixin staining.
- Radixin colocalization with MRP2 was restored upon improved bile drainage.
Conclusions:
- Disrupted MRP2-radixin colocalization is a common feature in cholestatic liver diseases.
- This disruption likely leads to MRP2 endocytic retrieval due to failed anchoring in the canalicular membrane.
