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Hypotonicity‐Induced WNK1 Phosphorylation Prevents H 2 O 2 ‐Induced Apoptosis in Vascular Smooth Muscle Cells

Yajuan Zhang, Wei Lin, Fengting Lu, Zhujun Liang, Chengcui Huang, Ma mingming, Liang Sijia, Pang Ruiping, Jiaguo Zhou, Yongyuan Guan, Guozheng Liang, Xiaofei Lv

Basic & Clinical Pharmacology & Toxicology · 2026

Vollständiger Abstract

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ABSTRACT 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 H 2 O 2 ‐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.

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Autor:innen
Yajuan Zhang, Wei Lin, Fengting Lu, Zhujun Liang, Chengcui Huang, Ma mingming, Liang Sijia, Pang Ruiping, Jiaguo Zhou, Yongyuan Guan, Guozheng Liang, Xiaofei Lv
Quelle
Basic & Clinical Pharmacology & Toxicology
Publikation
2026-01-01
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ISSN / ISBN
1742-7835, 1742-7843
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Yajuan Zhang, Wei Lin, Fengting Lu, Zhujun Liang, Chengcui Huang, Ma mingming, Liang Sijia, Pang Ruiping, Jiaguo Zhou, Yongyuan Guan, Guozheng Liang, Xiaofei Lv (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
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