Cellular Physiology and Biochemistry

Original Paper

Free Access

Involvement of HIF-1α in MLCK-dependent Endothelial Barrier Dysfunction in Hypoxia

Qi H. · Wang P. · Liu C. · Li M. · Wang S. · Huang Y. · Wang F.

Author affiliations

State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Burn Research, Southwest Hospital, Third Military Medical University, Chongqing

Corresponding Author

Fengjun Wang

State Key Laboratory of Trauma, Burns and Combined Injury

Institute of Burn Research, Southwest Hospital, Third Military Medical University

30 Gaotanyan Street, Chongqing, 400038 (P. R. China)

Tel. +862368754176, Fax +862365460398, E-Mail wangfj@mail.tmmu.com.cn

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Abstract

The mechanisms of endothelial barrier dysfunction induced by hypoxia are incompletely understood. Hypoxia-inducible factor-1 alpha (HIF-1α) is a key transcription factor partially responsible for hypoxia-related responses, but its role in regulation of hypoxia-induced endothelial barrier dysfunction is unclear. The aim of this study was to determine the molecular mechanism by which HIF-1α regulates endothelial barrier function during hypoxia. Endothelial cell monolayers exposed to normoxia or hypoxia were used for physiological, morphological, and biochemical analyses. The results showed that hypoxia disrupts endothelial barrier function by upregulating protein expression of myosin light chain (MLC) kinase (MLCK) and MLC phosphorylation. Hypoxia also induces HIF-1 activation by increasing HIF-1α expression, nuclear accumulation, DNA binding activity and target gene expression of HIF-1 in endothelial cells. Knockdown of HIF-1α attenuates endothelial barrier dysfunction and the increased MLCK protein expression induced by hypoxia. Inhibiting the transcription activity of HIF-1 by overexpressing factor inhibiting HIF-1(FIH) prevents the increased MLC phosphorylation and also attenuates endothelial barrier dysfunction in hypoxia. The results suggest that HIF-1α is involved in the MLCK-dependent endothelial barrier dysfunction induced by hypoxia.

© 2011 S. Karger AG, Basel




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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Accepted: February 21, 2011
Published online: April 01, 2011
Issue release date: April 2011

Number of Print Pages: 12
Number of Figures: 0
Number of Tables: 0

ISSN: 1015-8987 (Print)
eISSN: 1421-9778 (Online)

For additional information: https://www.karger.com/CPB


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