title: Krüppel-like factor-11, a transcription factor involved in diabetes mellitus, suppresses endothelial cell activation via the nuclear factor-κB signaling pathway.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cardiovascular Center, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Fan
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Guo
authors.forename: Jifeng
authors.initials: J
authors.lastname: Zhang
authors.forename: Malayannan
authors.initials: M
authors.lastname: Subramaniam
authors.forename: Chao-Zhong
authors.initials: CZ
authors.lastname: Song
authors.forename: Raul
authors.initials: R
authors.lastname: Urrutia
authors.forename: Y Eugene
authors.initials: YE
authors.lastname: Chen
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins / Q000502:physiology*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D003920:Diabetes Mellitus / Q000503:physiopathology*; D019040:E-Selectin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000502:physiology*; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics; D012097:Repressor Proteins / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D019040:E-Selectin; C115117:KLF11 protein, human; C506460:KLF11 protein, mouse; D008070:Lipopolysaccharides; D016328:NF-kappa B; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D014157:Transcription Factors; D019010:Vascular Cell Adhesion Molecule-1; D019892:eIF-2 Kinase