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Crosstalk between TLR4 and Notch1 signaling in the IgA nephropathy during inflammatory response

  • Nephrology - Original Paper
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Abstract

Purpose

IgA nephropathy (IgAN) is an immune complex-mediated disease involved in the kidney disease. Recent studies have revealed that Notch signaling-related genes are aberrantly expressed in various cell types and maybe associate with inflammation-induced carcinogenesis. The aim of our study was to investigate the function of Notch1 in the inflammatory response of IgAN.

Methods

The expression of Notch1, Jagged1 and NICD1 in 52 IgAN renal tissues and 20 control renal tissues was first determined using quantitative real-time PCR and Western blot. ELISA was then used to estimate the inflammatory response of human podocytes to LPS. NF-κB activity was measured using dual-luciferase reporter assay. Activation of Notch1 and NF-κB signaling pathway was assessed using Western blot.

Results

The expression of Notch1, NICD1 and Jagged1 was significantly higher in IgAN renal tissues than control renal tissues (P < 0.05). LPS treatment resulted in an obvious increase of MCP-1, IL-8 and phosphorylated NF-κB p65 in podocytes polymeric IgA (pIgA) IgAN group compared to control group (P < 0.05 for all). Activated Notch1 and its target genes, Hes1 and Hey1 were also enhanced upon LPS stimulation. Silencing of Notch1 signaling with inhibitor DAPT, NF-κB activation and LPS-induced inflammatory response were obviously attenuated, whereas Notch1 activator Jagged1 could markedly restore NF-κB activity and LPS-induced inflammatory response (P < 0.05 for all).

Conclusions

Crosstalk between TLR4 and Notch1 signaling regulates the inflammatory response in the IgAN and maybe plays an important role in the progression of IgAN.

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Acknowledgements

We thank all the staff in the department of Nephrology of Linyi People’s Hospital for their help on the manuscript.

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Authors and Affiliations

  1. Department of Nephrology, Linyi People’s Hospital, Linyi, 276003, Shandong, People’s Republic of China

    Xuxiang Sheng, Xihui Liu & Xia Sun

  2. Department of Nephrology, Yiyuan People’s Hospital, Zibo, Shandong, People’s Republic of China

    Xiaoyan Zuo

  3. Department of Nephrology, Affiliated Hospital of Ningbo University Medical School, Ningbo, Zhejiang, People’s Republic of China

    Yang Zhou

Authors
  1. Xuxiang Sheng
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  2. Xiaoyan Zuo
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  3. Xihui Liu
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  4. Yang Zhou
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  5. Xia Sun
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Correspondence to Xihui Liu.

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The authors declare that they have no competing interests.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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Sheng, X., Zuo, X., Liu, X. et al. Crosstalk between TLR4 and Notch1 signaling in the IgA nephropathy during inflammatory response. Int Urol Nephrol 50, 779–785 (2018). https://doi.org/10.1007/s11255-017-1760-2

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  • DOI: https://doi.org/10.1007/s11255-017-1760-2

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