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Inflammatory factor-specific sumoylation regulates NF-κB signalling in glomerular cells from diabetic rats

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Abstract

Objective

The activation of nuclear factor (NF)-κB by cytokines under hyperglycaemic conditions is a potential mechanism for complications in diabetes. We investigated whether small ubiquitin-like modifier 4 (SUMO4) regulates renal NF-κB signalling in diabetic rats.

Methods

Histological changes in kidney were analysed in diabetic GK rats. The expressions of tumour necrosis factor (TNF)-α, NF-κB (p65), IκBα and SUMO4 in renal tissues were examined by immunohistochemistry and Western blotting. Primary cultured glomerular endothelial cells from rats were stimulated by TNF-α or interleukin (IL)-2.

Results

The renal expression of TNF-α, NF-κB (p65), IκBα and SUMO4 was significantly higher in diabetic GK rats than in control rats. In control rats, no nuclear translocation was observed for IκBα or NF-κB (p65). However, in diabetic GK rats, translocation of NF-κB (p65) and IκBα into the nucleus was observed, and the expression of SUMO4 and IκBα was up-regulated in the glomerular endothelial cells. SUMO4 was localised in both the cytoplasm and nucleus, while IκBα was predominantly located in the nucleus after stimulation with TNF-α. In contrast, SUMO4 was localised in the nucleus, and increased cytoplasm SUMO4 localisation was found after stimulation with IL-2.

Conclusions

SUMO4 plays a role in regulating NF-κB signalling in glomerular cells. Cytokines have a unique effect in regulating the sumoylation of NF-κB.

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Acknowledgments

We thank Lijuan Wang (Chongqing Institute of Hypertension, China) for technical assistance. This research was supported by grants from the National Basic Research Program of China (2012CB517806) and National Natural Science Foundation of China (81130006).

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Authors and Affiliations

  1. Department of Geriatric Disease, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China

    Sijiao Chen, Hongyan Li, Yinghua Guo, Hongyan Yang & Jinchun Xu

  2. Center for Hypertension and Metabolic and Endocrinology Diseases, Daping Hospital of Third Military Medical University, Chongqing, 400042, China

    Tao Yang, Zhiming Zhu & Daoyan Liu

  3. Key Laboratory of Cell Biology of Ministry of Health, Medical Molecular Biology Research Institute of China Medical University, Shenyang, 110001, China

    Furong Liu & Jindan Song

Authors
  1. Sijiao Chen
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  2. Tao Yang
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  3. Furong Liu
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  4. Hongyan Li
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  5. Yinghua Guo
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  6. Hongyan Yang
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  7. Jinchun Xu
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  8. Jindan Song
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  9. Zhiming Zhu
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  10. Daoyan Liu
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Corresponding authors

Correspondence to Sijiao Chen or Daoyan Liu.

Additional information

Responsible Editor: Liwu Li.

Sijiao Chen and Tao Yang contributed equally to this work.

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Chen, S., Yang, T., Liu, F. et al. Inflammatory factor-specific sumoylation regulates NF-κB signalling in glomerular cells from diabetic rats. Inflamm. Res. 63, 23–31 (2014). https://doi.org/10.1007/s00011-013-0675-3

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  • DOI: https://doi.org/10.1007/s00011-013-0675-3

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