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Articles by C. E Cowan
Total Records ( 1 ) for C. E Cowan
  C. E Cowan , E. E Kohler , T. A Dugan , M. K Mirza , A. B Malik and K. K. Wary
  Rationale:

Vascular endothelial (VE)-cadherin localized at adherens junctions (AJs) regulates endothelial barrier function. Because WNT (wingless) signaling-induced activation of the transcription factor Krüppel-like factor (KLF)4 may have an important role in mediating the expression of VE-cadherin and AJ integrity, we studied the function of KLF4 in regulating VE-cadherin expression and the control of endothelial barrier function.

Objective:

The goal of this study was to determine the transcriptional role of KLF4 in regulating VE-cadherin expression and endothelial barrier function.

Methods and Results:

Expression analysis, microscopy, chromatin immunoprecipitation, electrophoretic mobility shift assays, and VE-cadherin–luciferase reporter experiments demonstrated that KLF4 interacted with specific domains of VE-cadherin promoter and regulated the expression of VE-cadherin at AJs. KLF4 knockdown disrupted the endothelial barrier, indicating that KLF4 is required for normal barrier function. In vivo studies in mice showed augmented lipopolysaccharide-induced lung injury and pulmonary edema following Klf4 depletion.

Conclusion:

Our data show the key role of KLF4 in the regulation of VE-cadherin expression at the level of the AJs and in the acquisition of VE-cadherin–mediated endothelial barrier function. Thus, KLF4 maintains the integrity of AJs and prevents vascular leakage in response to inflammatory stimuli.

 
 
 
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