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  • Hypoxia-inducible factor 1alpha modulates adhesion, migration, and FAK phosphorylation in vascular smooth muscle cells.

Hypoxia-inducible factor 1alpha modulates adhesion, migration, and FAK phosphorylation in vascular smooth muscle cells.

Journal of cellular biochemistry (2005-09-09)
Katina M Corley, Caroline J Taylor, Brenda Lilly
ABSTRACT

Hypoxia promotes angiogenesis by modulating the transcriptional regulator hypoxia-inducible factor 1alpha (HIF-1alpha). HIF-1alpha is a master regulator of the hypoxic response, and its proangiogenic activities include, but are not limited to, regulation of vascular endothelial growth factor (VEGF). The remodeling of the vasculature during angiogenesis requires an initial destabilization step, which facilitates endothelial sprouting, followed by vessel growth, and restabilization through investment of smooth muscle cells. The complex dynamics of hypoxia-induced angiogenesis prompted us to investigate what aspects of this multi-step process are regulated by HIF-1alpha. To do so, we analyzed the molecular properties of aortic and coronary artery smooth muscle cells in response to forced expression of HIF-1alpha, and by treatment with cobalt chloride, which mimics hypoxia. Our results demonstrate that HIF-1alpha causes a marked reduction in the ability of smooth muscle cells to migrate and adhere to extracellular matrices. Analysis of focal adhesion proteins showed no significant difference in expression or localization of vinculin or focal adhesion kinase (FAK). However, investigation of FAK phosphorylation, a critical mediator of adhesion and migration, revealed tyrosine phosphorylation of FAK is diminished in the presence of HIF-1alpha and cobalt chloride. These results indicate that during hypoxia-induced vessel remodeling, HIF-1alpha functions to dampen adhesion and migration of smooth muscle cells by modulating FAK activity. We suggest that HIF-1alpha expression in smooth muscle cells may augment vessel sprouting by loosening smooth muscle cell attachments to the basement membrane and endothelial cells.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
HIF-1 α N-terminal activation domain (530-698) human, recombinant, expressed in E. coli, ≥80% (SDS-PAGE)
Sigma-Aldrich
HIF-1 α, C-terminal activation domain (776-826 human, recombinant, expressed in E. coli, ≥85% (SDS-PAGE)