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Inhibition of semaphorin-3a suppresses lipopolysaccharide-induced acute kidney injury

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Abstract

Semaphorin-3a (Sema3A), a soluble axon guidance cue, appears to play an important role in the development of acute kidney injury (AKI) and has been regarded as an early diagnostic marker to evaluate the progression of AKI. However, the role of Sema3A in sepsis-associated AKI remains unknown. In this study, lipopolysaccharide (LPS) was used to simulate sepsis-associated AKI and the role of Sema3A in LPS-induced AKI was investigated in vivo and in vitro. In our in vivo study, Sema3A was found in tubular epithelial cells (TECs), which presented a higher level after LPS treatment. Meanwhile, the results of our in vitro experiment showed that Sema3A was also elevated in NRK-52E cells treated by LPS. Notably, inhibition of Sema3A by (−)-epigallocatechin-3-gallate (EGCG) could significantly reduce kidney inflammation and apoptosis in mice. Likewise, EGCG intervention also ameliorated the inflammation and apoptosis of cells in vitro. Furthermore, our research also found that the Rac1/NF-κB p65 and JNK pathways were possibly involved in the Sema3A-mediated inflammation and apoptosis of TECs, respectively. Our findings suggest that Sema3A play a pathogenic role by promoting inflammation and apoptosis of TECs in LPS-induced AKI. It might serve as a useful treatment target in ameliorating sepsis-associated AKI.

Key messages

  • Sema3A is upregulated in LPS-induced AKI.

  • Inhibition of Sema3A attenuates inflammation and apoptosis of TECs in LPS-induced AKI.

  • Sema3A enhances the LPS-induced inflammation of TECs through the Rac1/NF-κB p65 pathway.

  • Sema3A exacerbates the LPS-induced apoptosis of TECs through the JNK pathway.

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Acknowledgments

We sincerely thank Lixue Chen, Wenhui Yan, Xiaojuan Deng, and Guangchen Qin of the Central Laboratory of the First Affiliated Hospital of Chongqing Medical University for their assistance with these experiments.

Funding

This study was supported by Wu Jieping Medical Foundation (No. 320.6750.16196) and the Medical Research and Developmental Fund of the First Affiliated Hospital of Chongqing Medical University (No. PYJJ2017-02).

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Authors and Affiliations

  1. Department of Nephrology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, China

    Xiaofang Tian, Hua Gan, Hongfei Zhao & Yunfeng Xia

  2. Department of Urology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, China

    Yizhou Zeng

  3. Department of Cardiology, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, China

    Rong Tang

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  1. Xiaofang Tian
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Correspondence to Yunfeng Xia.

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Tian, X., Gan, H., Zeng, Y. et al. Inhibition of semaphorin-3a suppresses lipopolysaccharide-induced acute kidney injury. J Mol Med 96, 713–724 (2018). https://doi.org/10.1007/s00109-018-1653-6

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  • DOI: https://doi.org/10.1007/s00109-018-1653-6

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