ArticleKidney international2019
RNA-Seq and protein mass spectrometry in microdissected kidney tubules reveal signaling processes initiating lithium-induced nephrogenic diabetes insipidus.
Article in Kidney international, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24 citing papers in PubMed, 33 citations in OpenAlex.
- The lithium-magnesium-zinc axis under stress: regulation of N-glycosylation-linked proteostasis and Alzheimer's disease.Inflammopharmacology · 2026Review
- Energy metabolism in the kidney and its role in chronic kidney disease.Clinical and experimental nephrology · 2026Review
- Uric acid reduces the expression of aquaporins in renal collecting ducts to increase urine output in hyperuricemia.Frontiers in physiology · 2025Article
- Phosphoproteomic response to epidermal growth factor in native rat inner medullary collecting duct.American journal of physiology. Renal physiology · 2025Article
- A Possible Link between Cell Plasticity and Renin Expression in the Collecting Duct: A Narrative Review.International journal of molecular sciences · 2024Review
- 'Aquaporin-omics': mechanisms of aquaporin-2 loss in polyuric disorders.The Journal of physiology · 2024Article
- Article
- Collecting duct water permeability inhibition by EGF is associated with decreased cAMP, PKA activity, and AQP2 phosphorylation at SerAmerican journal of physiology. Renal physiology · 2024Article
- Sex differences in renal transporters: assessment and functional consequences.Nature reviews. Nephrology · 2024Review
- Autophagy and regulation of aquaporins in the kidneys.Kidney research and clinical practice · 2023Article
- Signaling mechanisms in renal compensatory hypertrophy revealed by multi-omics.Nature communications · 2023Article
- Long non-coding RNA DLX6-AS1 is the key mediator of glomerular podocyte injury and albuminuria in diabetic nephropathy by targeting the miR-346/GSK-3β signaling pathway.Cell death & disease · 2023Article
- Reduction of lithium induced interstitial fibrosis on co-administration with amiloride.Scientific reports · 2022Article
- Systems Biology of the Vasopressin V2 Receptor: New Tools for Discovery of Molecular Actions of a GPCR.Annual review of pharmacology and toxicology · 2022Review
- Over-Dose Lithium Toxicity as an Occlusive-like Syndrome in Rats and Gastric Pentadecapeptide BPC 157.Biomedicines · 2021Article
- Bayesian identification of candidate transcription factors for the regulation ofAmerican journal of physiology. Renal physiology · 2021Article
- Phosphoproteomic Identification of Vasopressin/cAMP/Protein Kinase A-Dependent Signaling in Kidney.Molecular pharmacology · 2021Review
- The tissue proteome in the multi-omic landscape of kidney disease.Nature reviews. Nephrology · 2021Review
- Multimodal Imaging Mass Spectrometry: Next Generation Molecular Mapping in Biology and Medicine.Journal of the American Society for Mass Spectrometry · 2020Review
- Role of Aquaporins in Inflammation-a Scientific Curation.Inflammation · 2020Review
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10 authors at 4 institutions in 3 countries.
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Abstract
Lithium salts, used for treating bipolar disorder, frequently induce nephrogenic diabetes insipidus (NDI) thereby limiting therapeutic success. NDI is associated with loss of expression of the gene coding for the molecular water channel, aquaporin-2, in the renal collecting duct (CD). Here, we use systems biology methods in a well-established rat model of lithium-induced NDI to identify signaling pathways activated at the onset of polyuria. Using single-tubule RNA-Seq, full transcriptomes were determined in microdissected cortical collecting ducts (CCDs) of rats after 72 hours without or with initiation of lithium chloride administration. Transcriptome-wide changes in mRNA abundances were mapped to gene sets associated with curated canonical signaling pathways, showing evidence for activation of NF-κB signaling with induction of genes coding for multiple chemokines and most components of the Major Histocompatibility Complex Class I antigen-presenting complex. Administration of anti-inflammatory doses of dexamethasone to lithium chloride-treated rats countered the loss of aquaporin-2. RNA-Seq also confirmed prior evidence of a shift from quiescence into the cell cycle with arrest. Time course studies demonstrated an early (12 hour) increase in multiple immediate early response genes including several transcription factors. Protein mass spectrometry in microdissected CCDs provided corroborative evidence and identified decreased abundance of several anti-oxidant proteins. Thus, in the context of prior observations, our study can be best explained by a model in which lithium increases ERK activation leading to induction of NF-κB signaling and an inflammatory-like response that represses Aqp2 transcription.
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