Thymosin Beta-4, Actin-Sequestering Protein Regulates Vascular Endothelial Growth Factor Expression via Hypoxia-Inducible Nitric Oxide Production in HeLa Cervical Cancer Cells.
10.4062/biomolther.2014.101
- Author:
Yun Kyoung RYU
1
;
Jae Wook LEE
;
Eun Yi MOON
Author Information
1. Department of Bioscience and Biotechnology, Sejong University, Seoul 143-747, Republic of Korea. eunyimoon@sejong.ac.kr
- Publication Type:Original Article
- Keywords:
VEGF;
Thymosin beta-4;
Nitric oxide;
Hypoxia;
HIF-1alpha
- MeSH:
Actins;
Anoxia;
Nitric Oxide Synthase;
Nitric Oxide*;
omega-N-Methylarginine;
Plasmids;
Response Elements;
RNA;
Thymosin*;
Transfection;
Uterine Cervical Neoplasms*;
Vascular Endothelial Growth Factor A*
- From:Biomolecules & Therapeutics
2015;23(1):19-25
- CountryRepublic of Korea
- Language:English
-
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.
