Chronic lithium treatment induces novel patterns of pendrin localization and expression

• Published in: American journal of physiology. Renal physiology Vol. 315; no. 2; pp. F313 - F322
• Main Authors: Himmel, Nathaniel J, Wang, Yirong, Rodriguez, Daniel A, Sun, Michael A, Blount, Mitsi A
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.08.2018
• Subjects: Adenosine triphosphatase; Ammonium Compounds - urine; Animals; Aquaporin 4; Aquaporin 4 - metabolism; Cell Plasticity - drug effects; Cell Proliferation - drug effects; Chloride-Bicarbonate Antiporters - genetics; Chloride-Bicarbonate Antiporters - metabolism; Collecting duct; Diet; Drug Administration Schedule; Gene expression; Gene Expression Regulation; H+-transporting ATPase; Homeostasis; Hydrogen-Ion Concentration; Kidney Tubules, Collecting - drug effects; Kidney Tubules, Collecting - metabolism; Kidney Tubules, Collecting - pathology; Kidneys; Lithium; Lithium Carbonate - toxicity; Localization; Male; Osmolar Concentration; Phenotype; Phenotypes; Polyuria - chemically induced; Polyuria - pathology; Polyuria - urine; Rats, Sprague-Dawley; Rodents; Side effects; Signal Transduction; Sulfate Transporters - genetics; Sulfate Transporters - metabolism; Time Factors; Urine; Vacuolar Proton-Translocating ATPases - metabolism; lithium; pendrin; diabetes insipidus; acid-base homeostasis; acidosis
• ISSN: 1931-857X; 1522-1466; 1522-1466
• DOI: 10.1152/ajprenal.00065.2018

Prolonged lithium treatment is associated with various renal side effects and is known to induce inner medullary collecting duct (IMCD) remodeling. In animals treated with lithium, the fraction of intercalated cells (ICs), which are responsible for acid-base homeostasis, increases compared with renal principal cells (PCs). To investigate the intricacies of lithium-induced IMCD remodeling, male Sprague-Dawley rats were fed a lithium-enriched diet for 0,1, 2, 3, 6, 9, or 12 wk. Urine osmolality was decreased at 1 wk, and from 2 to 12 wk, animals were severely polyuric. After 6 wk of lithium treatment, approximately one-quarter of the cells in the initial IMCD expressed vacuolar H -ATPase, an IC marker. These cells were localized in portions of the inner medulla, where ICs are not normally found. Pendrin, a Cl /[Formula: see text] exchanger, is normally expressed only in two IC subtypes found in the convoluted tubule, the cortical collecting duct, and the connecting tubule. At 6 wk of lithium treatment, we observed various patterns of pendrin localization and expression in the rat IMCD, including a novel phenotype wherein pendrin was coexpressed with aquaporin-4. These observations collectively suggest that renal IMCD cell plasticity may play an important role in lithium-induced IMCD remodeling.