Identification of oxidative stress-induced gene expression profiles in cavernosal endothelial cells

Hu,Chao; Dong,Yin‑Ying; Dong,Ye‑Hao; Cui,Jie‑Feng; Dai,Ji‑Can

doi:10.3892/mmr.2014.3112

Identification of oxidative stress-induced gene expression profiles in cavernosal endothelial cells

Authors:
- Chao Hu
- Yin‑Ying Dong
- Ye‑Hao Dong
- Jie‑Feng Cui
- Ji‑Can Dai
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Affiliations: Department of Urology, Affiliated Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, P.R. China, Department of Oncology, Institute of Liver Cancer, Affiliated Zhongshan Hospital, Fudan University, Shanghai 200032, P.R. China
Published online on: December 18, 2014 https://doi.org/10.3892/mmr.2014.3112
Pages: 2781-2788

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Abstract

The aim of the present study was to explore the regulation status of genes in oxidative stress (OS)‑induced endothelial dysfunction and to elucidate the mechanism of action of OS‑associated genes, which induce cavernosal endothelial dysfunction in erectile dysfunction (ED). OS was established in purified cavernosal endothelial cells (CECs) using xanthine/xanthine oxidase and the differentially expressed OS‑associated genes were analyzed using gene microarrays. In addition, an ED rat model was established through bilateral internal iliac artery ligation with hyperlipidemia and was verified by an intracavernosal pressure test. The selected OS‑associated genes were validated in the CECs and ED rat model using reverse transcription‑quantitative polymerase chain reaction. Student's t‑test and one‑way analysis of variance were performed using SBC analysis system. Gene microarray analysis revealed that 13090 (31.92%) genes were expressed in the control group, whereas 12039 (29.35%) genes were expressed in the treated group. The cut‑off value for differential expression was set at 2.0 fold‑change and 2480 genes were found to be differentially expressed compared with the control group. Of these cells, 1454 were upregulated and 1026 were downregulated. Cluster analysis identified relevant cell signaling pathways that were hypothesized to be significant in OS‑associated endothelial dysfunction, including the cytokine‑cytokine receptor interactions, nitrogen metabolism, coagulation cascades and cell adherens. Cxcl12, Tgfbr1, Asns, Bdkrb1 and Cdh3 genes showed a corresponding variation in the CECs and ED rat model compared with the results of the gene microarray analysis. In conclusion, in the present study, the network of differentially expressed genes and OS‑associated signaling pathways identified using gene microarray analysis were validated in the CECs and ED rat model. The results indicated that OS may lead to endothelial dysfunction through certain cell signaling pathways, inducing ED. However, further functional verification is required in order to elucidate the underlying mechanisms of OS‑associated cell signaling pathways in ED.

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