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UBR3 promotes inflammation and apoptosis via DUSP1/p38 pathway in the nucleus pulposus cells of patients with intervertebral disc degeneration

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Abstract

Intervertebral disc disease (IDD) is a primary cause of low back pain, affecting 5% of individuals. Previous study have shown that dual-specificity (Thr/Tyr) phosphatase 1 (DUSP1) regulates p38 MAPK activity and DUSP1 level is regulated by ubiquitination. As an E3 ubiquitin-protein ligase, UBR3 has been shown to regulate a variety of biological processes through ubiquitination. However, the role of UBR3/DUSP1/p38 in IDD remains to be elucidated. In the current study, we found that UBR3 was significantly increased in the nucleus pulposus tissues of IDD patients and was correlated with IDD severity. Silencing UBR3 promoted the growth, inhibited apoptosis, and inhibited inflammation in primary NPCs. Mechanism study suggested that UBR3 exerted its effects through p38. Co-immunoprecipitation assay indicated that UBR3 promoted DUSP1 ubiquitination. Overexpression of DUSP1 reversed the effect of UBR3 overexpression. Our data also supported that UBR3 was positively correlated with p-p38, but negatively correlated with DUSP1 in IDD. In summary, UBR3 promotes inflammation and apoptosis via inhibiting the p38 signaling pathway by DUSP1 ubiquitination in the NPCs of IDD patients. These findings highlight the importance of UBR3/DUSP1/p38 signaling pathway in IDD and provide new insights for the prevention and treatment of IDD.

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All data generated or analyzed during this study are included in this published article and its supplementary information files.

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Funding

This research was funded by Jiangsu Health International Exchange Program of Jiangsu Commission of Health (JSH-2018-017) and scientific research project of Jiangsu Commission of Health (Z2020006).

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  1. Zhenhuan Jiang and Qinghua Zhao contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopaedics, The Affiliated Yixing Hospital of Jiangsu University, Yixing, China

    Zhenhuan Jiang, Liang Chen, Lei Shen & Qiang Wang

  2. Department of Orthopaedics, School of Medicine, Shanghai First People’s Hospital, Shanghai Jiaotong University, Shanghai, China

    Qinghua Zhao

  3. Department of Radiology, The Affiliated Yixing Hospital of Jiangsu University, Yixing, China

    Yifeng Luo & Zhihong Cao

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  1. Zhenhuan Jiang
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  2. Qinghua Zhao
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  3. Liang Chen
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  4. Yifeng Luo
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  5. Lei Shen
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  7. Qiang Wang
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All authors made substantial contributions to conception and design, acquisition of data, interpretation of data, and writing the article.

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Correspondence to Zhihong Cao or Qiang Wang.

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The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki, and was approved by the Institutional Ethical Review Committee of the Affiliated Yixing Hospital of Jiangsu University. All patients filled out informed consent forms before sampling.

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Jiang, Z., Zhao, Q., Chen, L. et al. UBR3 promotes inflammation and apoptosis via DUSP1/p38 pathway in the nucleus pulposus cells of patients with intervertebral disc degeneration. Human Cell 35, 792–802 (2022). https://doi.org/10.1007/s13577-022-00693-6

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