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EGR1 transcriptionally regulates SVEP1 to promote proliferation and migration in human coronary artery smooth muscle cells

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Abstract

A low-frequency variant of sushi, von Willebrand factor type A, EGF, and pentraxin domain-containing protein 1 (SVEP1) is associated with the risk of coronary artery disease, as determined by a genome-wide association study. SVEP1 induces vascular smooth muscle cell proliferation and an inflammatory phenotype to promote atherosclerosis. In the present study, qRT‒PCR demonstrated that the mRNA expression of SVEP1 was significantly increased in atherosclerotic plaques compared to normal tissues. Bioinformatics revealed that EGR1 was a transcription factor for SVEP1. The results of the luciferase reporter assay, siRNA interference or overexpression assay, mutational analysis and ChIP confirmed that EGR1 positively regulated the transcriptional activity of SVEP1 by directly binding to its promoter. EGR1 promoted human coronary artery smooth muscle cell (HCASMC) proliferation and migration via SVEP1 in response to oxidized low-density lipoprotein (ox-LDL) treatment. Moreover, the expression level of EGR1 was increased in atherosclerotic plaques and showed a strong linear correlation with the expression of SVEP1. Our findings indicated that EGR1 binding to the promoter region drive SVEP1 transcription to promote HCASMC proliferation and migration.

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Data availability

The data in the current study are available. The WB images in Supporting Fig. 5 were uploaded.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (81970579 to GZP, 82101816 to QC, 82270068 to RJ) and the Natural Science Foundation of Jiangsu Province (BK20210965 to QC).

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Authors and Affiliations

  1. Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

    Qiang Tian, Jia-He Chen, Xin-Yu Wang, Jia-Yun Qiu, Qian Cao, Li-Li Zhuang, Rui Jin & Guo-Ping Zhou

  2. Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

    Yi Ding

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  1. Qiang Tian
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  2. Jia-He Chen
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Contributions

Qiang Tian, Jia-He Chen, and Yi Ding wrote the main manuscript. Xin-Yu Wang, Jia-Yun Qiu and Li–Li Zhuang assisted in the methodology. Qian Cao, Rui Jin and Guo-Ping Zhou received funding for the study and led the study. All authors reviewed the manuscript.

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Correspondence to Guo-Ping Zhou.

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The authors declare no competing interests.

Ethical approval

The study was approved by the Clinical Research Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (2016-SR-144). Informed consent was obtained from patients before participation.

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Tian, Q., Chen, JH., Ding, Y. et al. EGR1 transcriptionally regulates SVEP1 to promote proliferation and migration in human coronary artery smooth muscle cells. Mol Biol Rep 51, 365 (2024). https://doi.org/10.1007/s11033-024-09322-x

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