The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Activating transcription factor 4 aggravates angiotensin II-induced cell dysfunction in human vascular aortic smooth muscle cells via transcriptionally activating fibroblast growth factor 21

  • Tao, Ke (Department of General Surgery, Changshu Hospital Affiliated to Soochow University) ;
  • Li, Ming (Department of General Surgery, Changshu Hospital Affiliated to Soochow University) ;
  • Gu, Xuefeng (Department of General Surgery, Changshu Hospital Affiliated to Soochow University) ;
  • Wang, Ming (Department of General Surgery, Changshu Hospital Affiliated to Soochow University) ;
  • Qian, Tianwei (Department of General Surgery, Changshu Hospital Affiliated to Soochow University) ;
  • Hu, Lijun (Department of General Surgery, Changshu Hospital Affiliated to Soochow University) ;
  • Li, Jiang (Department of Vascular Surgery, The Affiliated Suzhou Hospital of Nanjing Medical University)
  • Received : 2022.04.21
  • Accepted : 2022.06.01
  • Published : 2022.09.01
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Abstract

Abdominal aortic aneurysm (AAA) is a life-threatening disorder worldwide. Fibroblast growth factor 21 (FGF21) was shown to display a high level in the plasma of patients with AAA; however, its detailed functions underlying AAA pathogenesis are unclear. An in vitro AAA model was established in human aortic vascular smooth muscle cells (HASMCs) by angiotensin II (Ang-II) stimulation. Cell counting kit-8, wound healing, and Transwell assays were utilized for measuring cell proliferation and migration. RT-qPCR was used for detecting mRNA expression of FGF21 and activating transcription factor 4 (ATF4). Western blotting was utilized for assessing protein levels of FGF21, ATF4, and markers for the contractile phenotype of HASMCs. ChIP and luciferase reporter assays were implemented for identifying the binding relation between AFT4 and FGF21 promoters. FGF21 and ATF4 were both upregulated in Ang-II-treated HASMCs. Knocking down FGF21 attenuated Ang-II-induced proliferation, migration, and phenotype switch of HASMCs. ATF4 activated FGF21 transcription by binding to its promoter. FGF21 overexpression reversed AFT4 silencing-mediated inhibition of cell proliferation, migration, and phenotype switch. ATF4 transcriptionally upregulates FGF21 to promote the proliferation, migration, and phenotype switch of Ang-II-treated HASMCs.

Keywords

Acknowledgement

This work was supported by Suzhou "Ke Jiao Xing Wei" Youth Science and Technology Development Program (No. KJXW2020064) and Changshu City Pharmaceutical Science and Technology Project (No. cswsq202001).

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