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Updated: Aug 16, 2026
Transcutaneous Assessment of Renal Function in Conscious Rodents
Published on: March 26, 2016
Up-regulation of Mrp4 expression in kidney of Mrp2-deficient TR- rats
Chuan Chen1, Angela L Slitt, Mathew Z Dieter
1Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
Abstract:
Multidrug resistance-associated proteins (Mrps) are a group of ATP-dependent efflux transporters for organic anions. Mrp2 and Mrp4 are co-localized to the apical (brush-border) membrane domain of renal proximal tubules, where they may function together in the urinary excretion of organic anions. Previous reports showed that urinary excretion of some organic anions is not impaired in transport-deficient (TR-) rats, which lack Mrp2, suggesting that up-regulation of other transporter(s) may compensate for the loss of Mrp2 function. The purpose of this study was to determine whether Mrp4 expression in kidney is altered in TR- rats. Mrp4 mRNA expression was quantified using the high-throughput branched DNA signal amplification assay. Mrp4 protein expression was determined by Western blot and immunohistochemical analysis. Mrp4 mRNA in kidney of TR- rats was 100% higher than normal Wistar rats. Western blot analysis showed a 200% increase in Mrp4 protein expression in kidney of the mutant rats compared to normal rats. Immunohistochemical analysis of Mrp4 protein demonstrated apical localization of Mrp4 on renal proximal tubules, and that the immunoreactivity was more intense in kidney sections from TR- rats than those from normal rats. In summary, the results of the present study demonstrate that renal Mrp4 expression is up-regulated in TR- rats, which may explain why urinary excretion of some organic anions remains normal in the mutant rats.
Insights
Multidrug resistance-associated protein 4 (Mrp4) expression increases in the kidneys of transport-deficient rats lacking Mrp2. This upregulation may compensate for Mrp2 loss, maintaining organic anion excretion.
Area of Science:
- Renal physiology and molecular transport mechanisms.
- Biochemistry of ATP-dependent efflux transporters.
Background:
- Multidrug resistance-associated proteins (Mrps) are ATP-dependent transporters crucial for organic anion excretion.
- Mrp2 and Mrp4 are localized to the apical membrane of renal proximal tubules, potentially collaborating in anion transport.
- Transport-deficient (TR-) rats lacking Mrp2 show unimpaired urinary excretion of some organic anions, suggesting compensatory mechanisms.
Purpose of the Study:
- To investigate alterations in Mrp4 expression within the kidney of TR- rats.
- To determine if Mrp4 expression is upregulated to compensate for the absence of Mrp2.
Main Methods:
- Quantification of Mrp4 mRNA using branched DNA signal amplification assay.
- Assessment of Mrp4 protein levels via Western blot analysis.
- Immunohistochemical analysis to determine Mrp4 protein localization and intensity in renal tissues.
Main Results:
- Mrp4 mRNA levels in TR- rat kidneys were 100% higher than in normal Wistar rats.
- Mrp4 protein expression was 200% higher in the kidneys of TR- rats compared to controls.
- Immunohistochemistry confirmed intense apical localization of Mrp4 in renal proximal tubules of TR- rats.
Conclusions:
- Renal Mrp4 expression is significantly upregulated in TR- rats.
- This compensatory upregulation of Mrp4 may explain the normal urinary excretion of certain organic anions in the absence of Mrp2.
