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LPS ameliorates renal ischemia/reperfusion injury via Hsp27 up-regulation

  • Nephrology - Original Paper
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Abstract

Purpose

We have recently reported lipopolysaccharide (LPS) pretreatment attenuated renal ischemia/reperfusion injury (IRI), but the exact mechanism remains to be well elucidated. It was reported that heat shock protein (Hsp) 27 was up-regulated after administration of LPS, but whether a direct link existed between Hsp27 up-regulation and LPS-induced protection against renal IRI is still unknown.

Methods

Mice were exposed to IRI or sham procedure, with pretreatment of LPS or not. Quercetin, an inhibitor of Hsp27 synthesis, was used, and an RNA interference with adenovirus vector using short hairpin RNA targeting Hsp27 was developed for inhibition of Hsp27 in mice. In addition, mice trans-infected with adenovirus vector encoding Hsp27 were used to testify the role of Hsp27 overexpression in LPS-induced renoprotection. Renal function, histological damage, inflammatory reaction, oxidative stress and apoptosis indices were measured. Western blot analysis was used to detect expression of Hsp27.

Results

We found LPS pretreatment stimulated renal up-regulation of Hsp27 and reduced renal IRI proven by less renal dysfunction, histological damage, inflammatory reaction, oxidative stress and apoptosis. It was observed that inhibition of Hsp27 synthesis by Quercetin abolished LPS-induced renoprotective effects. After renal knockdown of Hsp27, LPS-induced tolerance against renal IRI was largely removed. Mice with Hsp27 overexpression showed significantly improved renal function after IRI and LPS combined with Hsp27 overexpression had a synergistic effect on protection against renal IRI.

Conclusion

Administration of LPS produces protective effects against renal IRI via Hsp27 up-regulation. Preconditional Hsp27 up-regulation might have a great potential for the treatment of renal IRI via ameliorating apoptosis.

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Acknowledgements

This work was supported by grants from Shanghai Municipal Commission of Health and Family Planning (20124Y130) and the National Natural Science Foundation of China (Grant Number: 81270558). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

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  1. Kang He and Lei Xia contributed equally to this work.

Authors and Affiliations

  1. Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

    Kang He, Lei Xia & Jianjun Zhang

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  1. Kang He
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Correspondence to Jianjun Zhang.

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Ethical approval

All applicable international, national and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of Shanghai Jiaotong University School of Medicine and the Regulations for Practice of Experimental Animals (issued by Scientific and Technical Committee, P. R. China, 1988). All the procedures described were approved by the Animal Use and Care Committee of Shanghai Jiaotong University School of Medicine (Approval Number: SYKX-2008-0050).

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He, K., Xia, L. & Zhang, J. LPS ameliorates renal ischemia/reperfusion injury via Hsp27 up-regulation. Int Urol Nephrol 50, 571–580 (2018). https://doi.org/10.1007/s11255-017-1735-3

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