ArticleJournal of the American Society of Nephrology : JASN2014
Lithium causes G2 arrest of renal principal cells.
Article in Journal of the American Society of Nephrology : JASN, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Molecular mechanisms in lithium-associated renal disease: a systematic review.International urology and nephrology · 2016Pooled it
- Lithium effects on renal functioning: an expert opinion and management algorithm.International journal of bipolar disorders · 2026Article
- Lithium-induced kidney injury and fibrosis: A versatile model to explore cellular pathways of injury and repair.Physiological reports · 2025Review
- Absence of E-Cadherin and β-Catenin in the Basal Plasma Membrane of Collecting Duct Cells During NDI Development and Recovery.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2023Article
- Mechanistic insights into the primary and secondary alterations of renal ion and water transport in the distal nephron.Journal of internal medicine · 2023Review
- Reduction of lithium induced interstitial fibrosis on co-administration with amiloride.Scientific reports · 2022Article
- Sulfatide with ceramide composed of phytosphingosine (t18:0) and 2-hydroxy FAs in renal intercalated cells.Journal of lipid research · 2022Article
- Phosphoproteomic Identification of Vasopressin/cAMP/Protein Kinase A-Dependent Signaling in Kidney.Molecular pharmacology · 2021Review
- Article
- Predicted Cellular and Molecular Actions of Lithium in the Treatment of Bipolar Disorder: An In Silico Study.CNS drugs · 2020Article
- RNA-Seq and protein mass spectrometry in microdissected kidney tubules reveal signaling processes initiating lithium-induced nephrogenic diabetes insipidus.Kidney international · 2019Article
- Chronic lithium treatment induces novel patterns of pendrin localization and expression.American journal of physiology. Renal physiology · 2018Article
- Genetic Deletion of P2YFrontiers in physiology · 2018Article
- Deletion of β1-integrin in collecting duct principal cells leads to tubular injury and renal medullary fibrosis.American journal of physiology. Renal physiology · 2017Article
- In Vitro Cytotoxic and Anticancer Effects of Zamzam Water in Human Lung Cancer (A594) Cell Line.The Malaysian journal of medical sciences : MJMS · 2017Article
- Role of adenylyl cyclase 6 in the development of lithium-induced nephrogenic diabetes insipidus.JCI insight · 2017Article
- Article
- What we need to know about the effect of lithium on the kidney.American journal of physiology. Renal physiology · 2016Review
- Acetazolamide Attenuates Lithium-Induced Nephrogenic Diabetes Insipidus.Journal of the American Society of Nephrology : JASN · 2016Article
- Lithium in the Kidney: Friend and Foe?Journal of the American Society of Nephrology : JASN · 2016Review
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vasopressin-regulated expression and insertion of aquaporin-2 channels in the luminal membrane of renal principal cells is essential for urine concentration. Lithium affects urine concentrating ability, and approximately 20% of patients treated with lithium develop nephrogenic diabetes insipidus (NDI), a disorder characterized by polyuria and polydipsia. Lithium-induced NDI is caused by aquaporin-2 downregulation and a reduced ratio of principal/intercalated cells, yet lithium induces principal cell proliferation. Here, we studied how lithium-induced principal cell proliferation can lead to a reduced ratio of principal/intercalated cells using two-dimensional and three-dimensional polarized cultures of mouse renal collecting duct cells and mice treated with clinically relevant lithium concentrations. DNA image cytometry and immunoblotting revealed that lithium initiated proliferation of mouse renal collecting duct cells but also increased the G2/S ratio, indicating G2/M phase arrest. In mice, treatment with lithium for 4, 7, 10, or 13 days led to features of NDI and an increase in the number of principal cells expressing PCNA in the papilla. Remarkably, 30%-40% of the PCNA-positive principal cells also expressed pHistone-H3, a late G2/M phase marker detected in approximately 20% of cells during undisturbed proliferation. Our data reveal that lithium treatment initiates proliferation of renal principal cells but that a significant percentage of these cells are arrested in the late G2 phase, which explains the reduced principal/intercalated cell ratio and may identify the molecular pathway underlying the development of lithium-induced renal fibrosis.
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