Tumor necrosis factor-alpha and the ERK Pathway drive chemerin expression in response to hypoxia in cultured human coronary artery endothelial cells

Su Kiat Chua, Kou-Gi Shyu, Yuh-Feng Lin, Huey Ming Lo, Bao Wei Wang, Hang Chang, Li-Ming Lien

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

Background Chemerin, a novel adipokine, plays a role in the inflammation status of vascular endothelial cells. Hypoxia causes endothelial-cell proliferation, migration, and angiogenesis. This study was aimed at evaluating the protein and mRNA expression of chemerin after exposure of human coronary artery endothelial cells (HCAECs) to hypoxia. Methods and Results Cultured HCAECs underwent hypoxia for different time points. Chemerin protein levels increased after 4 h of hypoxia at 2.5% O2 , with a peak of expression of tumor necrosis factor-alpha (TNF-alpha) at 1 h. Both hypoxia and exogenously added TNF-alpha during normoxia stimulated chemerin expression, whereas an ERK inhibitor (PD98059), ERK small interfering RNA (siRNA), or an anti-TNF-alpha antibody attenuated the chemerin upregulation induced by hypoxia. A gel shift assay indicated that hypoxia induced an increase in DNA-protein binding between the chemerin promoter and transcription factor SP1. A luciferase assay confirmed an increase in transcriptional activity of SP1 on the chemerin promoter during hypoxia. Hypoxia significantly increased the tube formation and migration of HCAECs, whereas PD98059, the anti-TNF-alpha antibody, and chemerin siRNA each attenuated these effects. Conclusion Hypoxia activates chemerin expression in cultured HCAECs. Hypoxia-induced chemerin expression is mediated by TNF-alpha and at least in part by the ERK pathway. Chemerin increases early processes of angiogenesis by HCAECs after hypoxic treatment.

Original languageEnglish
Article numbere0165613
JournalPLoS One
Volume11
Issue number10
DOIs
Publication statusPublished - Oct 1 2016

ASJC Scopus subject areas

  • General Medicine
  • General Biochemistry,Genetics and Molecular Biology
  • General Agricultural and Biological Sciences

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