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Molecular biology reports
Feb 26, 2024;51 (1): 365.

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

Qiang Tian, Jia-He Chen, Yi Ding, Xin-Yu Wang, Jia-Yun Qiu, Qian Cao, Li-Li Zhuang, Rui Jin, Guo-Ping Zhou
Author Information
  1. Qiang Tian: Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  2. Jia-He Chen: Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  3. Yi Ding: Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  4. Xin-Yu Wang: Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  5. Jia-Yun Qiu: Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  6. Qian Cao: Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  7. Li-Li Zhuang: Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  8. Rui Jin: Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
  9. Guo-Ping Zhou: Department of Pediatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. gpzhou2017@126.com.
PMID: 38409611 DOI: 10.1007/s11033-024-09322-x

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.

Keywords

Atherosclerosis EGR1 Migration Proliferation SVEP1 Transcriptional regulation

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Grants

  1. 82101816/National Natural Science Foundation of China
  2. 82270068/National Natural Science Foundation of China
  3. 81970579/National Natural Science Foundation of China
  4. BK20210965/Natural Science Foundation of Jiangsu Province

MeSH Term

Humans
Plaque, Atherosclerotic
Coronary Vessels
Genome-Wide Association Study
Cell Movement
Lipoproteins, LDL
Cells, Cultured
Cell Proliferation
Myocytes, Smooth Muscle
MicroRNAs
Early Growth Response Protein 1
Cell Adhesion Molecules

Chemicals

Lipoproteins, LDL
MicroRNAs
EGR1 protein, human
Early Growth Response Protein 1
SVEP1 protein, human
Cell Adhesion Molecules
Journal Article

Word Cloud

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