{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:05:24Z","timestamp":1791313524355,"version":"4.3.1"},"reference-count":42,"publisher":"Portland Press Ltd.","issue":"19","license":[{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,10,8]]},"abstract":"<jats:p>Vascular smooth muscle cell (VSMC) phenotypic switching, followed by enhanced proliferation and migration, is a key event in the development of intimal hyperplasia in diverse vascular diseases. While tetraspanin 4 (TSPAN4) is known to be expressed in the vasculature, its function in VSMC phenotypic switching and vascular disease is currently unknown. Here, we investigated the role of TSPAN4 using an in vitro model of platelet-derived growth factor BB (PDGF-BB)-induced phenotypic switching and an in vivo carotid artery ligation model in wildtype and TSPAN4-deficient mice. Our experiments, including EdU assays, Transwell assays, western blot analysis, and immunoprecipitation, revealed that TSPAN4 expression is elevated in human atherosclerotic arteries, ligated mouse carotid arteries, and PDGF-BB-stimulated VSMCs. Additionally, TSPAN4 overexpression promoted the switch from a contractile to a synthetic phenotype, accompanied by enhanced VSMC proliferation and migration. Conversely, TSPAN4 knockdown inhibited these effects, suppressing PDGF-BB-induced phenotypic switching. Mechanistically, TSPAN4 was found to interact with and influence the expression and localization of tropomyosin-1 (TPM1). This, in turn, affected cytoskeletal organization, ultimately driving phenotypic switching and functional alterations in VSMCs. Finally, we demonstrated that TSPAN4 deficiency in mice attenuated vascular neointimal formation following carotid artery ligation. These findings suggested that TSPAN4 is a promising novel therapeutic target for vascular remodeling and proliferative vascular diseases.<\/jats:p>","DOI":"10.1042\/cs20255833","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T13:37:09Z","timestamp":1759930629000},"page":"1145-1161","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["TSPAN4 controls vascular smooth muscle cell phenotypic switching and intimal hyperplasia by targeting TPM1-regulated cytoskeletal organization"],"prefix":"10.1042","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0229-6856","authenticated-orcid":false,"given":"Shengbiao","family":"Li","sequence":"first","affiliation":[{"name":"1School of Basic Medical Sciences, Nucleic Acid Medicine of Luzhou Key Laboratory, Basic Medicine Research Innovation Center for Cardiometabolic Diseases, Southwest Medical University, Luzhou, Sichuan, 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kexin","family":"Chen","sequence":"additional","affiliation":[{"name":"1School of Basic Medical Sciences, Nucleic Acid Medicine of Luzhou Key Laboratory, Basic Medicine Research Innovation Center for Cardiometabolic Diseases, Southwest Medical University, Luzhou, Sichuan, 646000, China"},{"name":"2Department of Cardiology, West China Hospital, Sichuan University, Chengdu, 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[{"name":"1School of Basic Medical Sciences, Nucleic Acid Medicine of Luzhou Key Laboratory, Basic Medicine Research Innovation Center for Cardiometabolic Diseases, Southwest Medical University, Luzhou, Sichuan, 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yu","sequence":"additional","affiliation":[{"name":"3Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Nucleic Acid Medicine of Luzhou Key Laboratory, Key Laboratory of Medical Electrophysiology, Ministry of Education, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"1School of Basic Medical Sciences, Nucleic Acid Medicine of Luzhou Key Laboratory, Basic Medicine Research Innovation Center for Cardiometabolic Diseases, Southwest Medical University, Luzhou, Sichuan, 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghui","family":"Jiang","sequence":"additional","affiliation":[{"name":"1School of Basic Medical Sciences, Nucleic Acid Medicine of Luzhou Key Laboratory, Basic Medicine Research Innovation Center for Cardiometabolic Diseases, Southwest Medical University, Luzhou, Sichuan, 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi","family":"Li","sequence":"additional","affiliation":[{"name":"1School of Basic Medical Sciences, Nucleic Acid Medicine of Luzhou Key Laboratory, Basic Medicine Research Innovation Center for Cardiometabolic Diseases, Southwest Medical University, Luzhou, Sichuan, 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubo","family":"Fu","sequence":"additional","affiliation":[{"name":"1School of Basic Medical Sciences, Nucleic Acid Medicine of Luzhou Key Laboratory, Basic Medicine Research Innovation Center for Cardiometabolic Diseases, Southwest Medical University, Luzhou, Sichuan, 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"chen","sequence":"additional","affiliation":[{"name":"1School of Basic Medical Sciences, Nucleic Acid Medicine of Luzhou Key Laboratory, Basic Medicine Research Innovation Center for Cardiometabolic Diseases, Southwest Medical University, Luzhou, Sichuan, 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiapan","family":"Li","sequence":"additional","affiliation":[{"name":"1School of Basic Medical Sciences, Nucleic Acid Medicine of Luzhou Key Laboratory, Basic Medicine Research Innovation Center for Cardiometabolic Diseases, Southwest Medical University, Luzhou, Sichuan, 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyan","family":"Yi","sequence":"additional","affiliation":[{"name":"1School of Basic Medical Sciences, Nucleic Acid Medicine of Luzhou Key Laboratory, Basic Medicine Research Innovation Center for Cardiometabolic Diseases, Southwest Medical University, Luzhou, Sichuan, 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Li","sequence":"additional","affiliation":[{"name":"4Basic Medicine Research Innovation Center for Cardiometabolic Diseases, Ministry of Education; Luzhou Municipal Key Laboratory of Thrombosis and Vascular Biology; Laboratory for Cardiovascular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gan","family":"Qiao","sequence":"additional","affiliation":[{"name":"5Department of Pharmacology, School of Pharmacy, Nucleic Acid Medicine of Luzhou Key Laboratory, Central Nervous System Drug Key Laboratory of Sichuan Province, Southwest Medical University, Luzhou, Sichuan, 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianguo","family":"Feng","sequence":"additional","affiliation":[{"name":"6Anesthesiology and Critical Care Medicine Key Laboratory of Luzhou, the Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan Province, 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Jiang","sequence":"additional","affiliation":[{"name":"7Department of General Surgery (Thyroid Surgery), the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiong","family":"yuan","sequence":"additional","affiliation":[{"name":"3Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Nucleic Acid Medicine of Luzhou Key Laboratory, Key Laboratory of Medical Electrophysiology, Ministry of Education, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1914-2856","authenticated-orcid":false,"given":"Chunxiang","family":"Zhang","sequence":"additional","affiliation":[{"name":"3Department of Cardiology, The Affiliated Hospital of Southwest Medical University, Nucleic Acid Medicine of Luzhou Key Laboratory, Key Laboratory of Medical Electrophysiology, Ministry of Education, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, 646000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"2025100809370054500_CS-2025-5833C1","doi-asserted-by":"crossref","DOI":"10.1186\/s12964-022-00993-2","article-title":"How vascular smooth muscle cell phenotype switching contributes to vascular disease","volume":"20","author":"Cao","year":"2022","journal-title":"Cell Commun. 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