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Abstract: PO1102

Lithium Treatment Induces Changes in E-Cadherin, β-Catenin, and Na+/K+-ATPase β1 in Rat Inner Medullary Collecting Duct in a Time-Dependent Manner

Session Information

Category: Fluid, Electrolyte, and Acid-Base Disorders

  • 901 Fluid, Electrolyte, and Acid-Base Disorders: Basic

Authors

  • Sørtvedt, Xabier, Aarhus Universitet Institut for Biomedicin, Aarhus, Midtjylland, Denmark
  • Praetorius, Jeppe, Aarhus Universitet Institut for Biomedicin, Aarhus, Midtjylland, Denmark
  • Christensen, Birgitte Moenster, Aarhus Universitet Institut for Biomedicin, Aarhus, Midtjylland, Denmark
Background

Lithium (Li)-induced Nephrogenic Diabetes Insipidus (NDI) develops in around 40% of psychiatric patients receiving Li treatment. NDI is characterized by the inability of the kidney to concentrate urine due to insufficient water reabsorption in the kidney collecting duct (CD). Studies in rats have shown that Li induces a cellular compositional change of the CD with a fractional decrease in the ratio of principal-to-intercalated cells after 4 weeks of Li. This cellular remodeling is reversible in rats undergoing recovery for 19 days following 4 weeks of Li treatment. We aimed to investigate if regulation of the cell-contacts E-cadherin and β-catenin have a role in the cellular remodeling. The Na+/K+-ATPase was also investigated due to previously shown influences on cell polarity and cell-contact formation in kidney cells (Rajasekaran et al, Mol Biol Cell, 2001).

Methods

Immunohistochemistry (IHC) was performed on rat kidney sections used in previously published studies (Christensen et al, AJP, 2006; Trepiccione et al, AJP, 2013). Sections from rats treated with Li for 4, 10 and 15 days and 4 weeks were stained using antibodies against the cytoplasmic domain of E-cadherin, β-catenin and Na+/K+-ATPase β1-subunit. Sections from rats that had undergone recovery for 6 and 12 days following 4 weeks of Li treatment were stained for β-catenin.

Results

E-cadherin and β-catenin labeled basal and lateral plasma membrane domains in the inner medullary CD (IMCD). In the proximal part of IMCD, the labeling was absent from the basal plasma membrane domains of multiple cells after 4 and 10 days of Li treatment and was present again after 4 weeks of Li. In addition, the basal labeling of β-catenin was absent from some cells after 12 days of recovery. IHC of the Na+/K+-ATPase β1-subunit revealed a similar subcellular localization, and the protein was not present in the basal plasma membrane domains of multiple cells in the proximal part of the IMCD already after 4 days of Li.

Conclusion

The subcellular localization of the adherens junction proteins E-cadherin, β-catenin and Na+, K+-ATPase b1 is affected by Li treatment in the proximal part of the IMCD. In addition, the absence of labeling from the basal plasma membrane domains appears to occur prior to the cellular remodeling.

Funding

  • Private Foundation Support