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

Cell Reports (Aug 2023)

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

Journal volume & issue: Vol. 42, no. 8
p. 112869

Abstract

Read online

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.

CP: Cell biology

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

About the journal

Abstract

Keywords