ReviewHypertension research : official journal of the Japanese Society of Hypertension2020
The WNK signaling pathway and salt-sensitive hypertension.
Review in Hypertension research : official journal of the Japanese Society of Hypertension, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 45 citations in OpenAlex.
- Diet-induced obesity impairs salt-dependent downregulation of NCC activity.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Article
- Monogenic Kidney Disorders as Hidden Drivers of Electrolyte Imbalance and Hypertension.Electrolyte & blood pressure : E & BP · 2026Review
- WNK-SPAK-NKCC1/KCC2 pathway disrupts chloride homeostasis and drives hyperactivation of PVN-CRH neurons in essential hypertension.iScience · 2026Article
- With No-Lysine Kinase 1 Regulates Biotic and Abiotic Stress Tolerance in Rice by Targeting OsCATA to Alter HMolecular plant pathology · 2026Article
- Chloride Homeostasis Failure in Human Disease: KCC2/NKCC1 Microdomain Dysfunction as a Driver of Cortical Network Collapse.International journal of molecular sciences · 2026Review
- The genetics of hypertension.Nature reviews. Nephrology · 2026Review
- The roles, mechanisms, and therapeutic implications of glucocorticoids in glucose and lipid metabolism.Military Medical Research · 2026Review
- Oxidative Stress-Responsive 1 Kinase Catalytic Activity Promotes Triple Negative Breast Cancer Oncogenic Potential.ACS pharmacology & translational science · 2025Article
- Lenticulostriate vasculopathy in newborns: whole genome sequencing data analysis.Frontiers in pediatrics · 2025Article
- Sodium Chloride Cotransporter in Hypertension.Biomedicines · 2024Review
- Pathophysiological role of Na-Cl cotransporter in kidneys, blood pressure, and metabolism.Human cell · 2024Review
- Navigating the multifaceted intricacies of the NaPhysiological reviews · 2024Review
- CYLD alleviates NLRP3 inflammasome-mediated pyroptosis in osteoporosis by deubiquitinating WNK1.Journal of orthopaedic surgery and research · 2024Article
- Integrative single-cell characterization of a frugivorous and an insectivorous bat kidney and pancreas.Nature communications · 2024Article
- ClC-K Kidney Chloride Channels: From Structure to Pathology.Handbook of experimental pharmacology · 2024Article
- The role of uromodulin in cardiovascular disease: a review.Frontiers in cardiovascular medicine · 2024Review
- The Versatile Role of Uromodulin in Renal Homeostasis and Its Relevance in Chronic Kidney Disease.Internal medicine (Tokyo, Japan) · 2024Review
- Biomolecular condensates in kidney physiology and disease.Nature reviews. Nephrology · 2023Review
- Untargeted Metabolomics Analysis Using UHPLC-Q-TOF/MS Reveals Metabolic Changes Associated with Hypertension in Children.Nutrients · 2023Article
- Hypertensive heart disease: risk factors, complications and mechanisms.Frontiers in cardiovascular medicine · 2023Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The distal nephron of the kidney has a central role in sodium and fluid homeostasis, and disruption of this homeostasis due to mutations of with-no-lysine kinase 1 (WNK1), WNK4, Kelch-like 3 (KLHL3), or Cullin 3 (CUL3) causes pseudohypoaldosteronism type II (PHAII), an inherited hypertensive disease. WNK1 and WNK4 activate the NaCl cotransporter (NCC) at the distal convoluted tubule through oxidative stress-responsive gene 1 (OSR1)/Ste20-related proline-alanine-rich kinase (SPAK), constituting the WNK-OSR1/SPAK-NCC phosphorylation cascade. The level of WNK protein is regulated through degradation by the CUL3-KLHL3 E3 ligase complex. In the normal state, the activity of WNK signaling in the kidney is physiologically regulated by sodium intake to maintain sodium homeostasis in the body. In patients with PHAII, however, because of the defective degradation of WNK kinases, NCC is constitutively active and not properly suppressed by a high salt diet, leading to abnormally increased salt reabsorption and salt-sensitive hypertension. Importantly, recent studies have demonstrated that potassium intake, insulin, and TNFα are also physiological regulators of WNK signaling, suggesting that they contribute to the salt-sensitive hypertension associated with a low potassium diet, metabolic syndrome, and chronic kidney disease, respectively. Moreover, emerging evidence suggests that WNK signaling also has some unique roles in metabolic, cardiovascular, and immunological organs. Here, we review the recent literature and discuss the molecular mechanisms of the WNK signaling pathway and its potential as a therapeutic target.
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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.