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Abstract: FR-PO271

Imatinib-Associated Fluid Retention

Session Information

Category: Onconephrology

  • 1700 Onconephrology


  • Dave, Dhara, Yale School of Medicine, New Haven, Connecticut, United States
  • Abdelmalek, Kerolos N., Community Regional Medical Center, Fresno, California, United States
  • Dai, Zonghan, Texas Tech University Health Sciences Center School of Medicine, Amarillo, Texas, United States
  • Naguib, Tarek H., Texas Tech University Health Sciences Center School of Medicine, Amarillo, Texas, United States

Imatinib is one of the first tyrosine kinase inhibitors and is used in several conditions based on effects on receptors like BCR-ABL, the platelet-derived growth factor receptor (PDGFR), and stem cell factor (SCF)/c-kit tyrosine kinases. It has been associated with fluid retention (FR) and the mechanism behind this is largely unknown. Here we provide laboratory data that suggests imatinib affects aquaporin 2 (AQP2) expression proposing a theory behind imatinib associated FR.


Mouse kidney inner medullary collecting duct cell line (IMCD-3) cells are grown on coverslips in 24-well plate with DMEM containing 10% fetal bovine serum to 95% confluency. The cells are starved in 1 ml/well plain DMEM F12 medium for 2 hours prior to treatment. They are then treated with DMSO as control or with either 5 μM imatinib for 1 hour or 100 nM AVP for 30 min. After treatment, cells are washed, fixed, permeablized, and incubated with anti-aquaporin 2 antibody and Alexa Flor Goat anti-rabbit IgG 488. The cells are counter-stained by DAPI to visualize nuclei and stained coverslips then are mounted to slides and visualized under fluorescence microscope.


IMCD-3 cells express AQP2 with an even distribution in cytosol and membrane in untreated control cells. Stimulation of IMCD-3 with vasopressin promotes a dramatic membrane distribution of AQP2. Similar to vasopressin, treatment of IMCD-3 cells with imatinib also induced a profound membrane distribution.


To our knowledge, this is the first evidence that treatment of IMCD-3 with imatinib enhances AQP2 membrane distribution.
The bidirectional control of AQP2 trafficking from cytoplasm to the apical plasma membrane is regulated by vasopressin/vasopressin receptor (VP/VPR) pathway and filamentous actin (F-actin) polymerization/depolymerization. The signaling pathways can be activated by growth factor receptors such as EGFR and PDGFR which also cross-talk to VP/VPR. Abl tyrosine kinases likely play important roles as downstream receptors in regulating actin cytoskeleton remodeling and intracellular trafficking. Activation of Abl tyrosine kinases increases cell surface expression of EGFR. Therefore, inhibition of Abl tyrosine kinases by imatinib may lead to blockade of the EGF/EGFR signaling that regulates AQP2 distribution and FR.
Further study of Abl signaling as a potential regulator in AQP2 trafficking is warranted.


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