biostudies-literatureLi SApplied Basic Research Program of Sichuan ProvinceSichuan Province Science and Technology Support ProgramResearch Start-up Foundation of Southwest Medical UniversityNational Natural Science Foundation of ChinaSouthwest Medical UniversityScience and Technology Project of Luzhou GovernmentThe Central Government Guides Local Science and Technology Development ProjectNatural Science Foundation of Sichuan Province1145-1161https://www.ebi.ac.uk/biostudies/studies/S-EPMC12687436biostudies-literatureUnknown139(19)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 PDClinical science (London, England : 1979)TSPAN4 controls vascular smooth muscle cell phenotypic switching and intimal hyperplasia by targeting TPM1-regulated cytoskeletal organization.PMC126874362022YFS0627-A12021YJ020082030007, U23A203982022ZYD00572021ZKMS0052022YFS0578, 2022YFS0614,2022YFS0607,2022YFS0627000401552024NSFSC0580Qiao GJiang JFu SLi JChen KChen JYuan QLi RLi MYi JZhang TLi SFeng JZhang YJiang DZhang CYu YfalseTSPAN4 controls vascular smooth muscle cell phenotypic switching and intimal hyperplasia by targeting TPM1-regulated cytoskeletal organization.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 PD2025-01-01T00:00:00Z2025 Oct2026-06-06T00:12:28.021Z2026-05-23T03:13:58.659ZS-EPMC126874364100416210.1042/CS20255833