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http://dx.doi.org/10.4062/biomolther.2014.101

Thymosin Beta-4, Actin-Sequestering Protein Regulates Vascular Endothelial Growth Factor Expression via Hypoxia-Inducible Nitric Oxide Production in HeLa Cervical Cancer Cells  

Ryu, Yun-Kyoung (Department of Bioscience and Biotechnology, Sejong University)
Lee, Jae-Wook (Department of Bioscience and Biotechnology, Sejong University)
Moon, Eun-Yi (Department of Bioscience and Biotechnology, Sejong University)
Publication Information
Biomolecules & Therapeutics / v.23, no.1, 2015 , pp. 19-25 More about this Journal
Abstract
Vascular endothelial growth factor (VEGF) is an important regulator of neovascularization. Hypoxia inducible nitric oxide (NO) enhanced the expression of VEGF and thymosin beta-4 ($T{\beta}4$), actin sequestering protein. Here, we investigated whether NO-mediated VEGF expression could be regulated by $T{\beta}4$ expression in HeLa cervical cancer cells. Hypoxia inducible NO production and VEGF expression were reduced by small interference (si) RNA of $T{\beta}4$. Hypoxia response element (HRE)-luciferase activity and VEGF expression were increased by the treatment with N-(${\beta}$-D-Glucopyranosyl)-N2-acetyl-S-nitroso-D, L-penicillaminamide (SNAP-1), to generate NO, which was inhibited by the inhibition of $T{\beta}4$ expression with $T{\beta}4$-siRNA. In hypoxic condition, HRE-luciferase activity and VEGF expression were inhibited by the treatment with $N^G$-monomethyl-L-arginine (L-NMMA), an inhibitor to nitric oxide synthase (NOS), which is accompanied with a decrease in $T{\beta}4$ expression. VEGF expression inhibited by L-NMMA treatment was restored by the transfection with pCMV-$T{\beta}4$ plasmids for $T{\beta}4$ overexpression. Taken together, these results suggest that $T{\beta}4$ could be a regulator for the expression of VEGF via the maintenance of NOS activity.
Keywords
VEGF; Thymosin beta-4; Nitric oxide; Hypoxia; HIF-$1{\alpha}$;
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