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

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.