Potential role of recombinant adeno‑associated virus human thioredoxin‑PR39 in cell and vascular protection against hypoxia

Ruan,Xi‑Yun; Liang,Ying‑Chun; Du,Bin; Lin,You‑Ting; Guo,Yu‑Dong; Zhao,Jing; Li,Shan; Li,Ji‑Feng; Sun,Qin‑Jian; Du,Yi‑Feng

doi:10.3892/etm.2015.2301

Potential role of recombinant adeno‑associated virus human thioredoxin‑PR39 in cell and vascular protection against hypoxia

Authors:
- Xi‑Yun Ruan
- Ying‑Chun Liang
- Bin Du
- You‑Ting Lin
- Yu‑Dong Guo
- Jing Zhao
- Shan Li
- Ji‑Feng Li
- Qin‑Jian Sun
- Yi‑Feng Du
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Affiliations: Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China, Department of Neurology, The Central Hospital of Tai'an, Tai'an, Shandong 271000, P.R. China, Department of Neurosurgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China, Department of Neurosurgery, The Fifth Hospital of Jinan, Jinan, Shandong 250021, P.R. China, Department of Neurology, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China
Published online on: February 17, 2015 https://doi.org/10.3892/etm.2015.2301
Pages: 1605-1610
Copyright: © Ruan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to successfully construct a recombinant adeno‑associated virus (rAAV) vector containing the human thioredoxin (hTRX)‑PR39 chimeric gene (rAAV/hTRX‑PR39), and verify that the vector was able to maintain a sustained, stable and efficient expression to achieve protein production in the cell. In the present study, a chicken embryo model was utilized to analyze the therapeutical effect of rAAV/hTRX‑PR39 in cerebral ischemia diseases. ECV304 cells were transfected with rAAV/hTRX‑PR39 and incubated under conditions of 20, 5 and 1% O2. Subsequently, the expression levels of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGFR)‑1, VEGFR‑2, fibroblast growth factor receptor (FGFR)‑1 and syndecan‑4 were detected by reverse transcription‑quantitative polymerase chain reaction. Under hypoxic conditions, the mRNA expression levels of VEGF, VEGFR‑1, VEGFR‑2, FGFR‑1 and syndecan‑4 were found to increase in the PR39‑transfected group when compared with the control group, while no statistically significant difference was observed between the PR39‑transfected group and the control group under conditions of 20% O2. In addition, hTRX‑PR39 was shown to increase the density of the vasculature and the survival rate of the chick embryos. Under hypoxic conditions, it was hypothesized that rAAV/hTRX‑PR39 was capable of promoting angiogenesis, which may subsequently protect the cells from impairment by hypoxia. In conclusion, rAAV/hTRX‑PR39 was demonstrated to promote vascularization and cell survival in hypoxia; thus, rAAV/hTRX‑PR39 may have potential for use in therapy targeting cerebral ischemia.

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