Transcription Factor MEF2C Suppresses Endothelial Cell Inflammation via Regulation of NF-κB and KLF2

Zhenhua Xu, Takeshi Yoshida, Lijuan Wu, Debasish Maiti, Liudmila Cebotaru, Elia J. Duh

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


Endothelial cells play a major role in the initiation and perpetuation of the inflammatory process in health and disease, including their pivotal role in leukocyte recruitment. The role of pro-inflammatory transcription factors in this process has been well-described, including NF-κB. However, much less is known regarding transcription factors that play an anti-inflammatory role in endothelial cells. Myocyte enhancer factor 2C (MEF2C) is a transcription factor known to regulate angiogenesis in endothelial cells. Here, we report that MEF2C plays a critical function as an inhibitor of endothelial cell inflammation. Tumor necrosis factor (TNF)-α inhibited MEF2C expression in endothelial cells. Knockdown of MEF2C in endothelial cells resulted in the upregulation of pro-inflammatory molecules and stimulated leukocyte adhesion to endothelial cells. MEF2C knockdown also resulted in NF-κB activation in endothelial cells. Conversely, MEF2C overexpression by adenovirus significantly repressed TNF-α induction of pro-inflammatory molecules, activation of NF-κB, and leukocyte adhesion to endothelial cells. This inhibition of leukocyte adhesion by MEF2C was partially mediated by induction of KLF2. In mice, lipopolysaccharide (LPS)-induced leukocyte adhesion to the retinal vasculature was significantly increased by endothelial cell-specific ablation of MEF2C. Taken together, these results demonstrate that MEF2C is a novel negative regulator of inflammation in endothelial cells and may represent a therapeutic target for vascular inflammation. J. Cell. Physiol. 230: 1310-1320, 2015.

Original languageEnglish (US)
Pages (from-to)1310-1320
Number of pages11
JournalJournal of Cellular Physiology
Issue number6
StatePublished - Jun 1 2015

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology


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