ArticleScientific reports2016
An isoform of Nedd4-2 is critically involved in the renal adaptation to high salt intake in mice.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 21 citations in OpenAlex.
- Neuroligin-2 is ubiquitinated by Nedd4l to control developmental astrocyte morphogenesis.The Journal of cell biology · 2026Article
- Neuroligin-2 is ubiquitinated by Nedd4l to control developmental astrocyte morphogenesis.bioRxiv : the preprint server for biology · 2025Article
- Interpreting the efficacy enhancement mechanism of Chinese medicine processing from a biopharmaceutic perspective.Chinese medicine · 2024Review
- Nedd4-2-dependent regulation of astrocytic Kir4.1 and Connexin43 controls neuronal network activity.The Journal of cell biology · 2024Article
- Aldosterone Antagonism Is More Effective at Reducing Blood Pressure and Excessive Renal ENaC Activity in AngII-Infused Female Rats Than in Males.Hypertension (Dallas, Tex. : 1979) · 2023Article
- Associations of genetic variations in NEDD4L with salt sensitivity, blood pressure changes and hypertension incidence in Chinese adults.Journal of clinical hypertension (Greenwich, Conn.) · 2022Article
- Role of the Ubiquitin Proteasome System in the Regulation of Blood Pressure: A Review.International journal of molecular sciences · 2020Review
- Regulators of Epithelial Sodium Channels in Aldosterone-Sensitive Distal Nephrons (ASDN): Critical Roles of Nedd4L/Nedd4-2 and Salt-Sensitive Hypertension.International journal of molecular sciences · 2020Review
- Effects of rikkunshito on renal fibrosis and inflammation in angiotensin II-infused mice.Scientific reports · 2019Article
- Angiotensin II Type 1 Receptor-associated Protein Inhibits Angiotensin II-induced Insulin Resistance with Suppression of Oxidative Stress in Skeletal Muscle Tissue.Scientific reports · 2018Article
- Early Enhanced Leucine-RichBioMed research international · 2018Article
- Renal Tubular Ubiquitin-Protein Ligase NEDD4-2 Is Required for Renal Adaptation during Long-Term Potassium Depletion.Journal of the American Society of Nephrology : JASN · 2017Article
- An Isoform of Nedd4-2 Plays a Pivotal Role in Electrophysiological Cardiac Abnormalities.International journal of molecular sciences · 2017Article
- Eplerenone-Resistant Salt-Sensitive Hypertension in Nedd4-2 C2 KO Mice.International journal of molecular sciences · 2017Article
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9 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Epithelial sodium channels (ENaCs) play critical roles in the maintenance of fluid and electrolyte homeostasis, and their genetic abnormalities cause one type of hereditary salt-sensitive hypertension, Liddle syndrome. As we reported previously, both human and rodent Nedd4L/Nedd4-2 showed molecular diversity, with and without a C2 domain in their N-terminal. Nedd4L/Nedd4-2 isoforms with a C2 domain are hypothesized to be related closely to ubiquitination of ENaCs. We generated Nedd4-2 C2 domain knockout mice. We demonstrate here that loss of Nedd4-2 C2 isoform causes salt-sensitive hypertension under conditions of a high dietary salt intake in vivo. The knockout mice had reduced urinary sodium excretion, osmotic pressure and increased water intake and urine volume with marked dilatation of cortical tubules while receiving a high salt diet. To the contrary, there was no difference in metabolic data between wild-type and knockout mice receiving a normal control diet. In the absence of Nedd4-2 C2 domain, a high salt intake accelerated ENaC expression. Coimmunoprecipitation studies revealed suppressed ubiquitination for ENaC with a high salt intake. Taken together, our findings demonstrate that during a high oral salt intake the Nedd4-2 C2 protein plays a pivotal role in maintaining adaptive salt handling in the kidney.
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