ArticleThe Journal of clinical investigation2015
Integrated compensatory network is activated in the absence of NCC phosphorylation.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 95 citations in OpenAlex.
- A Randomized Trial of Distal Diuretics versus Dietary Sodium Restriction for Hypertension in Chronic Kidney Disease.Journal of the American Society of Nephrology : JASN · 2020Trial
- The kidney distal tubule potassium switch, modern diet and hypertension.Nature reviews. Nephrology · 2026Review
- Pendrin is upregulated by corticosterone and participates in its pressor response.American journal of physiology. Renal physiology · 2026Article
- Calcium-binding protein 39 in with-no-lysine kinase signaling and the modulation of renal tubular transport.Current opinion in nephrology and hypertension · 2025Review
- Cholangiocarcinoma PDHA1 succinylation suppresses macrophage antigen presentation via alpha-ketoglutaric acid accumulation.Nature communications · 2025Article
- Diuretics in patients with chronic kidney disease.Nature reviews. Nephrology · 2025Review
- Thick Ascending Limb Specific Inactivation of Myh9 and Myh10 Myosin Motors Results in Progressive Kidney Disease and Drives Sex-specific Cellular Adaptation in the Distal Nephron and Collecting Duct.Function (Oxford, England) · 2025Article
- Pendrin: linking acid base to blood pressure.Pflugers Archiv : European journal of physiology · 2024Review
- Dietary potassium stimulates Ppp1Ca-Ppp1r1a dephosphorylation of kidney NaCl cotransporter and reduces blood pressure.The Journal of clinical investigation · 2023Article
- Aldosterone: Renal Action and Physiological Effects.Comprehensive Physiology · 2023Article
- Dissociation of sodium-chloride cotransporter expression and blood pressure during chronic high dietary potassium supplementation.JCI insight · 2023Article
- Kidney ion handling genes and their interaction in blood pressure control.Bioscience reports · 2022Review
- Activation of 2-oxoglutarate receptor 1 (OXGR1) by α-ketoglutarate (αKG) does not detectably stimulate Pendrin-mediated anion exchange in Xenopus oocytes.Physiological reports · 2022Article
- Regulation of Blood Pressure and Salt Balance By Pendrin-Positive Intercalated Cells: Donald Seldin Lecture 2020.Hypertension (Dallas, Tex. : 1979) · 2022Review
- The ClJournal of human hypertension · 2021Article
- Regulatory control of the Na-Cl co-transporter NCC and its therapeutic potential for hypertension.Acta pharmaceutica Sinica. B · 2021Review
- WNK-SPAK/OSR1-NCC kinase signaling pathway as a novel target for the treatment of salt-sensitive hypertension.Acta pharmacologica Sinica · 2021Review
- Infrared thermal imaging associated with pain in laboratory animals.Experimental animals · 2021Review
- Mechanisms coupling sodium and magnesium reabsorption in the distal convoluted tubule of the kidney.Acta physiologica (Oxford, England) · 2021Review
- Urinary Extracellular Vesicles for Renal Tubular Transporters Expression in Patients With Gitelman Syndrome.Frontiers in medicine · 2021Article
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9 authors at 2 institutions in 1 country.
Funding
Abstract
Thiazide diuretics are used to treat hypertension; however, compensatory processes in the kidney can limit antihypertensive responses to this class of drugs. Here, we evaluated compensatory pathways in SPAK kinase-deficient mice, which are unable to activate the thiazide-sensitive sodium chloride cotransporter NCC (encoded by Slc12a3). Global transcriptional profiling, combined with biochemical, cell biological, and physiological phenotyping, identified the gene expression signature of the response and revealed how it establishes an adaptive physiology. Salt reabsorption pathways were created by the coordinate induction of a multigene transport system, involving solute carriers (encoded by Slc26a4, Slc4a8, and Slc4a9), carbonic anhydrase isoforms, and V-type H⁺-ATPase subunits in pendrin-positive intercalated cells (PP-ICs) and ENaC subunits in principal cells (PCs). A distal nephron remodeling process and induction of jagged 1/NOTCH signaling, which expands the cortical connecting tubule with PCs and replaces acid-secreting α-ICs with PP-ICs, were partly responsible for the compensation. Salt reabsorption was also activated by induction of an α-ketoglutarate (α-KG) paracrine signaling system. Coordinate regulation of a multigene α-KG synthesis and transport pathway resulted in α-KG secretion into pro-urine, as the α-KG-activated GPCR (Oxgr1) increased on the PP-IC apical surface, allowing paracrine delivery of α-KG to stimulate salt transport. Identification of the integrated compensatory NaCl reabsorption mechanisms provides insight into thiazide diuretic efficacy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.