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A1AR-mediated renal protection against ischemia/reperfusion injury is dependent on HSP27 induction

  • Nephrology - Original Paper
  • Published:
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Abstract

Purpose

A1 adenosine receptor (AR) activation has been demonstrated to attenuate renal ischemia/reperfusion injury (IRI), but the exact mechanism of this protection remains to be well elucidated.

Methods

Male C57BL/6 mice were used in the present study. Expression of heat shock protein (HSP) 27 and HSF-1 were detected using western blot analysis. An RNA interference with adenovirus vector using short hairpin RNA targeting HSP27 was developed. Together with renal IRI model, indicators of renal function, acute tubular necrosis, inflammation and apoptosis were measured in kidneys after 24-h reperfusion.

Results

We found activation of A1AR stimulated induction of HSP27 and its major transcriptional factor HSF-1. It was observed that renal inhibition of HSP27 abolished the renoprotective effects afforded by A1AR activation indicated by worse renal function, severer acute tubular necrosis and pro-inflammatory reaction. In addition, HSP27 induction by A1AR activation protects the kidney from IRI via suppressing cell apoptosis, proved by decreased caspase-3 activation and DNA fragmentation, which was also removed by inhibition of HSP27.

Conclusions

Activation of A1AR produces renoprotective effects via HSP27 induction. It suggests that preconditional HSP27 activation might have a great potential for the treatment of renal IRI.

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Funding

This study was supported by the Guangxi Province Project of Development and Application of Appropriate Medical Technology (No. S201645).

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Author notes

  1. Bin Xiong and Min Li contributed equally to this work.

Authors and Affiliations

  1. Department of Intensive Care Unit, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, People’s Republic of China

    Bin Xiong, Shulin Xiang & Lin Han

  2. Department of Gerontology, South Campus, Renji Hospital School of Medicine, Shanghai Jiaotong University, Shanghai, 200127, People’s Republic of China

    Min Li

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  1. Bin Xiong
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  2. Min Li
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Correspondence to Lin Han.

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Xiong, B., Li, M., Xiang, S. et al. A1AR-mediated renal protection against ischemia/reperfusion injury is dependent on HSP27 induction. Int Urol Nephrol 50, 1355–1363 (2018). https://doi.org/10.1007/s11255-018-1797-x

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