Thymosin β4 induces the expression of vascular endothelial growth factor (VEGF) in a hypoxia-inducible factor (HIF)-1α-dependent manner

被引:44
|
作者
Jo, Jin-Ok [1 ]
Kim, Su-Ryun [3 ]
Bae, Moon-Kyung [3 ]
Kang, Yun-Jeong [1 ]
Ock, Mee Sun [1 ]
Kleinman, Hynda K. [4 ]
Cha, Hee-Jae [1 ,2 ]
机构
[1] Kosin Univ, Dept Parasitol & Genet, Coll Med, Pusan 602703, South Korea
[2] Kosin Univ, Inst Med Sci, Coll Med, Pusan 602703, South Korea
[3] Pusan Natl Univ, Dept Physiol, Sch Dent, Pusan, South Korea
[4] Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH | 2010年 / 1803卷 / 11期
关键词
Thymosin beta 4; VEGF; HIF-1; alpha; Hypoxia; Angiogenesis; Protein stability; ACTIN-SEQUESTERING PROTEIN; FACTOR; 1-ALPHA; HAIR-GROWTH; BETA(4); GENE; METASTASIS; ACTIVATION; CELLS; STABILIZATION; CARCINOMA;
D O I
10.1016/j.bbamcr.2010.07.005
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Thymosin beta 4 has multi-functional roles in cell physiology, but little is known about its mechanism(s) of action. We previously reported that thymosin beta 4 stimulated angiogenesis through the induction of vascular endothelial growth factor (VEGF). To identify the mechanism of VEGF induction by thymosin beta 4, we have used a luciferase assay system with VEGF in the 5' promoter region. We also analyzed the effect of thymosin beta 4 on VEGF mRNA stability and on the expression and stability of hypoxia-inducible factor (HIF)-1 alpha. We found that thymosin beta 4 induces VEGF expression by an increase in the stability of HIF-1 alpha protein. Analysis of the expression patterns of thymosin beta 4 and HIF-1 alpha in colon cancer tissue microarray showed that thymosin beta 4 and HIF-1 alpha co-localized in these biopsies. These data show that thymosin beta 4 induces the expression of VEGF indirectly by increasing the protein stability of HIF-1 alpha. (C) 2010 Elsevier B.V. All rights reserved.
引用
收藏
页码:1244 / 1251
页数:8
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