Kruppel-like factor 2 regulates endothelial barrier function

Zhiyong Lin, Viswanath Natesan, Hong Shi, Fei Dong, Daiji Kawanami, Ganapati H. Mahabeleshwar, G. Brandon Atkins, Lalitha Nayak, Yingjie Cui, James H. Finigan, Mukesh K. Jain

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

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. Methods and 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, KLF 2+/- 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 H2O2 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 H2O2-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. Conclusion-: These observations identify KLF2 as a novel transcriptional regulator of vascular barrier function.

Original languageEnglish (US)
Pages (from-to)1952-1959
Number of pages8
JournalArteriosclerosis, thrombosis, and vascular biology
Volume30
Issue number10
DOIs
StatePublished - Oct 2010
Externally publishedYes

Keywords

  • Kruppel-like factor 2
  • barrier function
  • endothelium

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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