ArticleScientific reports2018
WNK1 regulates skeletal muscle cell hypertrophy by modulating the nuclear localization and transcriptional activity of FOXO4.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- WNK1 mediates M-CSF-induced macropinocytosis to enforce macrophage lineage fidelity.Nature communications · 2025Article
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- Oligonucleotide Therapeutics for Age-Related Musculoskeletal Disorders: Successes and Challenges.Pharmaceutics · 2023Review
- Shenqi Yanshen Formula (SQYSF) protects against chronic kidney disease by modulating gut microbiota.Bioengineered · 2022Article
- Resveratrol inhibits bile acid-induced gastric intestinal metaplasia via the PI3K/AKT/p-FoxO4 signalling pathway.Phytotherapy research : PTR · 2021Article
- Transcriptome analysis reveals the long intergenic noncoding RNAs contributed to skeletal muscle differences between Yorkshire and Tibetan pig.Scientific reports · 2021Article
- FOXO4 Inhibits the Migration and Metastasis of Colorectal Cancer by Regulating theFrontiers in cell and developmental biology · 2021Article
- The WNK signaling pathway and salt-sensitive hypertension.Hypertension research : official journal of the Japanese Society of Hypertension · 2020Review
- Article
- Current perspective on the regulation of FOXO4 and its role in disease progression.Cellular and molecular life sciences : CMLS · 2020Review
- Comparative Analysis of Skeletal Muscle Transcriptional Signatures Associated With Aerobic Exercise Capacity or Response to Training in Humans and Rats.Frontiers in endocrinology · 2020Article
- Do neurogenic and cancer-induced muscle atrophy follow common or divergent paths?European journal of translational myology · 2018Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
With-no-lysine (K) (WNK) kinases, which are mutated in the inherited form of hypertension pseudohypoaldosteronism type II, are essential regulators of membrane ion transporters. Here, we report that WNK1 positively regulates skeletal muscle cell hypertrophy via mediating the function of the pro-longevity transcription factor forkhead box protein O4 (FOXO4) independent of the conventional WNK signaling pathway linking SPS/STE20-related proline-alanine-rich kinase (SPAK)/oxidative stress response kinase 1 (OSR1) to downstream effector ion transporters. Small interfering RNA (siRNA)-mediated silencing of WNK1, but not SPAK/OSR1 kinases, induced myotube atrophy and remarkable increases in the mRNA expression of the muscle atrophy ubiquitin ligases MAFbx and MuRF1 in C2C12 mouse skeletal muscle cells. WNK1 silencing also increased FOXO4 nuclear localization, and co-transfection of Foxo4-targeted siRNA completely reversed the myotube atrophy and upregulation of atrogene transcription induced by WNK1 silencing. We further illustrated that WNK1 protein abundance in skeletal muscle was increased by chronic voluntary wheel running exercise (hypertrophic stimulus) and markedly decreased by adenine-induced chronic kidney disease (atrophic stimulus) in mice. These findings suggest that WNK1 is involved in the physiological regulation of mammalian skeletal muscle hypertrophy and atrophy via interactions with FOXO4. The WNK1-FOXO4 axis may be a potential therapeutic target in human diseases causing sarcopenia.
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