Biomol Ther.  2015 Jan;23(1):19-25. 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 YK
• Lee JW
• Moon EY

• KMID: 2380358
• DOI: http://doi.org/10.4062/biomolther.2014.101

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 (Tbeta4), actin sequestering protein. Here, we investigated whether NO-mediated VEGF expression could be regulated by Tbeta4 expression in HeLa cervical cancer cells. Hypoxia inducible NO production and VEGF expression were reduced by small interference (si) RNA of Tbeta4. 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 Tbeta4 expression with Tbeta4-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 Tbeta4 expression. VEGF expression inhibited by L-NMMA treatment was restored by the transfection with pCMV-Tbeta4 plasmids for Tbeta4 overexpression. Taken together, these results suggest that Tbeta4 could be a regulator for the expression of VEGF via the maintenance of NOS activity.

Keyword

VEGF; Thymosin beta-4; Nitric oxide; Hypoxia; HIF-1alpha

MeSH Terms

Actins
Anoxia
Nitric Oxide Synthase
Nitric Oxide*
omega-N-Methylarginine
Plasmids
Response Elements
RNA
Thymosin*
Transfection
Uterine Cervical Neoplasms*
Vascular Endothelial Growth Factor A*
Actins
Nitric Oxide
Nitric Oxide Synthase
RNA
Thymosin
Vascular Endothelial Growth Factor A
omega-N-Methylarginine