Hypotonicity-Induced WNK1 Phosphorylation Prevents H(2)O(2)-Induced Apoptosis in Vascular Smooth Muscle Cells.
Y, Z., W, L., F, L., Z, L., C, H., M, M., L, S., P, R., J, Z., & Y, G. (2026). Hypotonicity-Induced WNK1 Phosphorylation Prevents H(2)O(2)-Induced Apoptosis in Vascular Smooth Muscle Cells.. Basic & clinical pharmacology & toxicology. https://doi.org/10.1111/bcpt.70299
Y Z, W L, F L, Z L, C H, M M, et al. Hypotonicity-Induced WNK1 Phosphorylation Prevents H(2)O(2)-Induced Apoptosis in Vascular Smooth Muscle Cells.. Basic & clinical pharmacology & toxicology. 2026; doi: 10.1111/bcpt.70299
Y Z, W L, F L, et al. Hypotonicity-Induced WNK1 Phosphorylation Prevents H(2)O(2)-Induced Apoptosis in Vascular Smooth Muscle Cells.[J]. Basic & clinical pharmacology & toxicology. 2026. DOI: 10.1111/bcpt.70299.
@article{y2026,
author = {Zhang Y and Lin W and Lu F and Liang Z and Huang C and Mingming M and Sijia L and Ruiping P and Zhou J and Guan Y},
title = {Hypotonicity-Induced WNK1 Phosphorylation Prevents H(2)O(2)-Induced Apoptosis in Vascular Smooth Muscle Cells.},
journal = {Basic & clinical pharmacology & toxicology},
year = {2026},
doi = {10.1111/bcpt.70299},
note = {PMID: 42675813},
}
TY - JOUR AU - Zhang Y AU - Lin W AU - Lu F AU - Liang Z AU - Huang C AU - Mingming M AU - Sijia L AU - Ruiping P AU - Zhou J AU - Guan Y TI - Hypotonicity-Induced WNK1 Phosphorylation Prevents H(2)O(2)-Induced Apoptosis in Vascular Smooth Muscle Cells. T2 - Basic & clinical pharmacology & toxicology PY - 2026 DO - 10.1111/bcpt.70299 AN - PMID:42675813 ER -
Vascular smooth muscle cells (VSMCs) are essential for maintaining arterial wall integrity, with their associated apoptosis critically involved in cardiovascular diseases. Intracellular chloride anion (Cl-) dysregulation is closely linked to apoptosis. However, the underlying mechanism via chloride-sensitive kinases remains unclear. Here, we show that hypotonic stimulation activates volume-regulated chloride channels (VRCCs) and induces the phosphorylation of the chloride-sensitive kinase WNK1. Activated WNK1 protects VSMCs against H2O2-induced apoptosis by maintaining the Bcl-2/Bax balance, preserving mitochondrial membrane potential and inhibiting caspase-9/3 activation. These findings uncover a novel protective role of WNK1 in VRCC-mediated Cl- signalling and provide new perspectives for targeting chloride-sensitive kinases in the treatment of hypertension and related cardiovascular diseases. Vascular smooth muscle cells (VSMCs) employ a chloride‐mediated mechanism to counteract stress and prevent cell death. Upon hypotonic stimulation, volume‐regulated chloride channels activate the chloride‐sensitive kinase WNK1. This activation restores the balance of key mitochondrial proteins, preserves cellular energy integrity and ultimately inhibits the apoptosis cascade. This discovery elucidates a novel ion‐signalling defence mechanism critical for maintaining vascular wall integrity. It positions the chloride–WNK1 axis as a promising therapeutic target for mitigating hypertension and related cardiovascular pathologies.