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Comprehensive analysis of biological landscape of oxidative stress-related genes in diabetic erectile dysfunction

International Journal of Impotence Research (2023)Cite this article

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Abstract

Oxidative stress plays a pivotal role in the pathogenesis of diabetic erectile dysfunction, while specific mechanisms have not been illuminated. The study aims to reveal the genetic expression patterns of oxidative stress in diabetic erectile dysfunction. Transcriptome data of diabetic erectile dysfunction and oxidative stress-related genes (OSRGs) in the Gene Expression Omnibus database were downloaded and analyzed based on differential expression. Functional enrichment analyses were conducted to clarify the biological functions. A protein interaction framework was established, and significant gene profiles were validated in the cavernous endothelial cells, clinical patients, and rat models. A miRNA–OSRGs network was predicted and validated. The results were analyzed using Student’s t-test. The analysis screened 203 differentially expressed OSRGs (p < 0.05), which had a close association with oxidoreductase activities, glutathione metabolism, and autophagy. A four-gene signature comprised of EPS8L2 (p = 0.044), GSTA3 (p = 0.015), LOX (p < 0.001) and MGST1 (p = 0.002) was well validated and regarded as the hub OSRGs. Compared with the control group, notable increases and decreases were observed in the expressions of GSTA3 (3.683 ± 0.636 vs. 0.416 ± 0.507) and LOX (2.104 ± 1.895 vs. 18.804 ± 2.751) in the validated diabetic erectile dysfunction group. The hub OSRGs-related miRNAs participated in smooth muscle cell proliferation. Besides, miR-125a-3p (p = 0.034) and miR-138-2-3p (p = 0.012) were validated as promising oxidative stress-related miRNA biomarkers. Our findings revealed the genetic alternations of oxidative stress in diabetic erectile dysfunction. These results will be instructive to explore the molecular landscape and the potential treatment for diabetic erectile dysfunction.

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Fig. 1: The flow diagram of the study.
Fig. 2: Differentially expressed OSRGs analysis.
Fig. 3: Functional enrichment analysis of significant OSRGs.
Fig. 4: PPI network construction of significant OSRGs.
Fig. 5: The profiling of OSRGs in the cavernous endothelial cells and clinical patients.
Fig. 6: The profiling of hub OSRGs in DMED.
Fig. 7: Associations between DMED and autophagy.

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Data availability

The data that support the findings and codes in R software of this study are available on request from the corresponding author.

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Acknowledgements

The authors would like to thank the associated databases for the availability of the data. The present study was funded by grants from the Medical Science and Technology Research-related joint construction project of Henan Province (No. LHGJ20220343) and the National Natural Science Foundation of China (No. 82201775 and 82201758).

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  1. These authors contributed equally: Qingjun Meng, Yinwei Chen.

Authors and Affiliations

  1. Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China

    Qingjun Meng, Lingang Cui, Yinsheng Wei, Teng Li & Penghui Yuan

  2. Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China

    Yinwei Chen

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Contributions

Conceptualization and design: PY, YC, QM. Acquisition of data: PY, TS, YS. Writing—original draft: PY, YC. Funding acquisition: PY, YC. Data collection and analysis: PY, LC, TL, YS, ZJ. Review and editing: PY, YC, TS, LC, TL, ZY, QM. All authors read and approved the final manuscript.

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Correspondence to Penghui Yuan.

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Meng, Q., Chen, Y., Cui, L. et al. Comprehensive analysis of biological landscape of oxidative stress-related genes in diabetic erectile dysfunction. Int J Impot Res (2023). https://doi.org/10.1038/s41443-023-00814-1

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