Krüppel-like factor-11, a transcription factor involved in diabetes mellitus, suppresses endothelial cell activation via the nuclear factor-κB signaling pathway

Yanbo Fan, Yanhong Guo, Jifeng Zhang, Malayannan Subramaniam, Chao Zhong Song, Raul Urrutia, Y. Eugene Chen

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

OBJECTIVE-: Endothelial cell (EC) inflammatory status is critical to many vascular diseases. Emerging data demonstrate that mutations of Krüppel-like factor-11 (KLF11), a gene coding maturity-onset diabetes mellitus of the young type 7 (MODY7), contribute to the development of neonatal diabetes mellitus. However, the function of KLF11 in the cardiovascular system still remains to be uncovered. In this study, we aimed to investigate the role of KLF11 in vascular endothelial inflammation. METHODS AND RESULTS-: KLF11 is highly expressed in vascular ECs and induced by proinflammatory stimuli. Adenovirus-mediated KLF11 overexpression inhibits expression of tumor necrosis factors-α-induced adhesion molecules. Moreover, small interfering RNA-mediated KLF11 knockdown augments the proinflammatory status in ECs. KLF11 inhibits promoter activity of adhesion molecules induced by tumor necrosis factor-α and nuclear factor-κB p65 overexpression. Mechanistically, KLF11 potently inhibits nuclear factor-κB signaling pathway via physical interaction with p65. Furthermore, KLF11 knockdown results in increased binding of p65 to vascular cell adhesion molecule-1 and E-selectin promoters. At the whole organism level, KLF11 mice exhibit a significant increase in leukocyte recruitment to ECs after lipopolysaccharide administration. CONCLUSION-: Taken together, our data demonstrate for the first time that KLF11 is a suppressor of EC inflammatory activation, suggesting that KLF11 constitutes a novel potential molecular target for inhibition of vascular inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)2981-2988
Number of pages8
JournalArteriosclerosis, thrombosis, and vascular biology
Volume32
Issue number12
DOIs
StatePublished - Dec 1 2012

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Keywords

  • Krüppel like factor-11
  • adhesion molecules
  • atherosclerosis
  • endothelial cell
  • inflammation
  • nuclear factor-.B

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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