title: Kruppel-like factor 2 regulates endothelial barrier function.
abstract: OBJECTIVE
  A central function of the endothelium is to serve as a selective barrier that regulates fluid and solute exchange. Although perturbation of barrier function can contribute to numerous disease states, our understanding of the molecular mechanisms regulating this aspect of endothelial biology remains incompletely understood. Accumulating evidence implicates the Kruppel-like factor 2 (KLF2) as a key regulator of endothelial function. However, its role in vascular barrier function is unknown.
  
  
  RESULTS
  To assess the role of KLF2 in vascular barrier function in vivo, we measured the leakage of Evans blue dye into interstitial tissues of the mouse ear after treatment with mustard oil. By comparison with KLF2(+/+) mice, KLF2(+/-) mice exhibited a significantly higher degree of vascular leak. In accordance with our in vivo observation, adenoviral overexpression of KLF2 in human umbilical vein endothelial cells strongly attenuated the increase of endothelial leakage by thrombin and H(2)O(2) as measured by fluorescein isothiocyanate dextrans (FITC-dextran) passage. Conversely, KLF2 deficiency in human umbilical vein endothelial cells and primary endothelial cells derived from KLF2(+/-) mice exhibited a marked increase in thrombin and H(2)O(2)-induced permeability. Mechanistically, our studies indicate that KLF2 confers barrier-protection via differential effects on the expression of key junction protein occludin and modification of a signaling molecule (myosin light chain) that regulate endothelial barrier integrity.
  
  
  CONCLUSIONS
  These observations identify KLF2 as a novel transcriptional regulator of vascular barrier function.
authors.affiliation: University Hospitals Harrington-McLaughlin Heart and Vascular Institute and Case Cardiovascular Research Institute, Cleveland, OH 44106-7290, USA. zhiyong.lin@case.edu
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Lin
authors.forename: Viswanath
authors.initials: V
authors.lastname: Natesan
authors.forename: Hong
authors.initials: H
authors.lastname: Shi
authors.forename: Fei
authors.initials: F
authors.lastname: Dong
authors.forename: Daiji
authors.initials: D
authors.lastname: Kawanami
authors.forename: Ganapati H
authors.initials: GH
authors.lastname: Mahabeleshwar
authors.forename: G Brandon
authors.initials: GB
authors.lastname: Atkins
authors.forename: Lalitha
authors.initials: L
authors.lastname: Nayak
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Cui
authors.forename: James H
authors.initials: JH
authors.lastname: Finigan
authors.forename: Mukesh K
authors.initials: MK
authors.lastname: Jain
mesh_terms: D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051741:Kruppel-Like Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D018994:Myosin Light Chains / Q000502:physiology; D062793:Occludin; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology; D014162:Transfection
chemical_list: C096161:KLF2 protein, human; C498314:Klf2 protein, mouse; D051741:Kruppel-Like Transcription Factors; D008565:Membrane Proteins; D018994:Myosin Light Chains; C568985:OCLN protein, human; D062793:Occludin; C568986:Ocln protein, mouse; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D006861:Hydrogen Peroxide; D013917:Thrombin