Sox10 escalates vascular inflammation by mediating vascular smooth muscle cell transdifferentiation and pyroptosis in neointimal hyperplasia
Xin Xu,
Dan-Dan Zhang,
Peng Kong,
Ya-Kun Gao,
Xiao-Fu Huang,
Yu Song,
Wen-Di Zhang,
Rui-Juan Guo,
Chang-Lin Li,
Bo-Wen Chen,
Yue Sun,
Yong-Bo Zhao,
Fang-Yue Jia,
Xu Wang,
Fan Zhang,
Mei Han
Affiliations
Xin Xu
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China; Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, China; Key Laboratory of Medical Biotechnology of Hebei Province, Hebei Medical University, Shijiazhuang 050017, China
Dan-Dan Zhang
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China; Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, China; Key Laboratory of Medical Biotechnology of Hebei Province, Hebei Medical University, Shijiazhuang 050017, China
Peng Kong
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China; Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, China; Key Laboratory of Medical Biotechnology of Hebei Province, Hebei Medical University, Shijiazhuang 050017, China
Ya-Kun Gao
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China; Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, China; Key Laboratory of Medical Biotechnology of Hebei Province, Hebei Medical University, Shijiazhuang 050017, China
Xiao-Fu Huang
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China; Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, China; Key Laboratory of Medical Biotechnology of Hebei Province, Hebei Medical University, Shijiazhuang 050017, China
Yu Song
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China; Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, China; Key Laboratory of Medical Biotechnology of Hebei Province, Hebei Medical University, Shijiazhuang 050017, China
Wen-Di Zhang
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China; Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, China; Key Laboratory of Medical Biotechnology of Hebei Province, Hebei Medical University, Shijiazhuang 050017, China
Rui-Juan Guo
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China; Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, China; Key Laboratory of Medical Biotechnology of Hebei Province, Hebei Medical University, Shijiazhuang 050017, China
Chang-Lin Li
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China; Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, China; Key Laboratory of Medical Biotechnology of Hebei Province, Hebei Medical University, Shijiazhuang 050017, China
Bo-Wen Chen
Department of Cardiac Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050017, China
Yue Sun
Department of Cardiac Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050017, China
Yong-Bo Zhao
Department of Cardiac Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050017, China
Fang-Yue Jia
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China; Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, China; Key Laboratory of Medical Biotechnology of Hebei Province, Hebei Medical University, Shijiazhuang 050017, China
Xu Wang
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China; Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, China; Key Laboratory of Medical Biotechnology of Hebei Province, Hebei Medical University, Shijiazhuang 050017, China
Fan Zhang
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China; Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, China; Key Laboratory of Medical Biotechnology of Hebei Province, Hebei Medical University, Shijiazhuang 050017, China; Corresponding author
Mei Han
Department of Biochemistry and Molecular Biology, College of Basic Medicine, Hebei Medical University, Shijiazhuang 050017, China; Key Laboratory of Neural and Vascular Biology of Ministry of Education, Hebei Medical University, Shijiazhuang 050017, China; Key Laboratory of Medical Biotechnology of Hebei Province, Hebei Medical University, Shijiazhuang 050017, China; Corresponding author
Summary: Vascular smooth muscle cells (VSMCs) can transdifferentiate into macrophage-like cells in the context of sustained inflammatory injury, which drives vascular hyperplasia and atherosclerotic complications. Using single-cell RNA sequencing, we identify that macrophage-like VSMCs are the key cell population in mouse neointimal hyperplasia. Sex-determining region Y (SRY)-related HMG-box gene 10 (Sox10) upregulation is associated with macrophage-like VSMC accumulation and pyroptosis in vitro and in the neointimal hyperplasia of mice. Tumor necrosis factor α (TNF-α)-induced Sox10 lactylation in a phosphorylation-dependent manner by PI3K/AKT signaling drives transcriptional programs of VSMC transdifferentiation, contributing to pyroptosis. The regulator of G protein signaling 5 (RGS5) interacts with AKT and blocks PI3K/AKT signaling and Sox10 phosphorylation at S24. Sox10 silencing mitigates vascular inflammation and forestalls neointimal hyperplasia in RGS5 knockout mice. Collectively, this study shows that Sox10 is a regulator of vascular inflammation and a potential control point in inflammation-related vascular disease.
