{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T09:11:52Z","timestamp":1790154712232,"version":"4.0.1"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T00:00:00Z","timestamp":1788134400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81903598"],"award-info":[{"award-number":["81903598"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473916"],"award-info":[{"award-number":["82473916"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004608","name":"Natural Science Foundation of Jiangsu Province","doi-asserted-by":"publisher","award":["BK20250354"],"award-info":[{"award-number":["BK20250354"]}],"id":[{"id":"10.13039\/501100004608","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    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\n                    <jats:sup>\u2212<\/jats:sup>\n                    ) dysregulation is closely linked to apoptosis. However, the underlying mechanism via chloride\u2010sensitive kinases remains unclear. Here, we show that hypotonic stimulation activates volume\u2010regulated chloride channels (VRCCs) and induces the phosphorylation of the chloride\u2010sensitive kinase WNK1. Activated WNK1 protects VSMCs against H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    \u2010induced apoptosis by maintaining the Bcl\u20102\/Bax balance, preserving mitochondrial membrane potential and inhibiting caspase\u20109\/3 activation. These findings uncover a novel protective role of WNK1 in VRCC\u2010mediated Cl\n                    <jats:sup>\u2212<\/jats:sup>\n                    signalling and provide new perspectives for targeting chloride\u2010sensitive kinases in the treatment of hypertension and related cardiovascular diseases.\n                  <\/jats:p>","DOI":"10.1111\/bcpt.70299","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T05:03:53Z","timestamp":1788239033000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hypotonicity\u2010Induced WNK1 Phosphorylation Prevents H\n                    <sub>2<\/sub>\n                    O\n                    <sub>2<\/sub>\n                    \u2010Induced Apoptosis in Vascular Smooth Muscle Cells"],"prefix":"10.1111","volume":"139","author":[{"given":"Yajuan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Cardiac and Cerebral Vascular Research Center, Zhongshan School of Medicine Sun Yat\u2010sen University  Guangzhou Guangdong China"},{"name":"Department of Cardiovascular Surgery of the First Affiliated Hospital &amp; Institute for Cardiovascular Science, Suzhou Medical College Soochow University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Cardiac and Cerebral Vascular Research Center, Zhongshan School of Medicine Sun Yat\u2010sen University  Guangzhou Guangdong China"},{"name":"Orthepedic Department of the First Affiliated Hospital Guangdong Pharmaceutical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1962-0036","authenticated-orcid":false,"given":"Fengting","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Cardiac and Cerebral Vascular Research Center, Zhongshan School of Medicine Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4907-2173","authenticated-orcid":false,"given":"Zhujun","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Cardiac and Cerebral Vascular Research Center, Zhongshan School of Medicine Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengcui","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Cardiac and Cerebral Vascular Research Center, Zhongshan School of Medicine Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0237-0940","authenticated-orcid":false,"given":"Ma","family":"mingming","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Cardiac and Cerebral Vascular Research Center, Zhongshan School of Medicine Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4014-6325","authenticated-orcid":false,"given":"Liang","family":"Sijia","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Cardiac and Cerebral Vascular Research Center, Zhongshan School of Medicine Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pang","family":"Ruiping","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Cardiac and Cerebral Vascular Research Center, Zhongshan School of Medicine Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaguo","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Cardiac and Cerebral Vascular Research Center, Zhongshan School of Medicine Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongyuan","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Cardiac and Cerebral Vascular Research Center, Zhongshan School of Medicine Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3335-0915","authenticated-orcid":false,"given":"Guozheng","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Cardiac and Cerebral Vascular Research Center, Zhongshan School of Medicine Sun Yat\u2010sen University  Guangzhou Guangdong China"},{"name":"Department of Cardiovascular Surgery of the First Affiliated Hospital &amp; Institute for Cardiovascular Science, Suzhou Medical College Soochow University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6100-7539","authenticated-orcid":false,"given":"Xiaofei","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Cardiac and Cerebral Vascular Research Center, Zhongshan School of Medicine Sun Yat\u2010sen University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,31]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.112.198648"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI70025"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401\u2010024\u201001280\u20101"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1745\u20107254.2005.00061.x"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12576\u2010023\u201000889\u2010x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1677\/erc.1.00898"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12576\u2010023\u201000897\u2010x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00037.2007"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2006.04.008"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495\u2010013\u20100881\u2010z"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2005365"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.2005050"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2322135121"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.124.324366"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2017.56"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.121.18472"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2024.123342"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401\u2010020\u20100357\u2010y"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.70159"},{"key":"e_1_2_10_21_1","first-page":"G29","article-title":"Altered Regulation of Smooth Muscle Cell Proliferation and Apoptosis in Small Arteries of Spontaneously Hypertensive Rats","volume":"19","author":"D\u00edez J.","year":"1998","journal-title":"European Heart Journal"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010023\u201000629\u20104"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.res.76.2.168"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.111.235622"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1062844"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20051180"}],"container-title":["Basic &amp; Clinical Pharmacology &amp; Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcpt.70299","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bcpt.70299","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bcpt.70299","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T08:51:08Z","timestamp":1790153468000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bcpt.70299"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,31]]},"references-count":25,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1111\/bcpt.70299"],"URL":"https:\/\/doi.org\/10.1111\/bcpt.70299","archive":["Portico"],"relation":{},"ISSN":["1742-7835","1742-7843"],"issn-type":[{"value":"1742-7835","type":"print"},{"value":"1742-7843","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,31]]},"assertion":[{"value":"2026-01-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70299"}}