Annexin 1 mimetic peptide protects against renal ischemia/reperfusion injury in rats

Abstract

Inflammation is currently recognized as a key mechanism in the pathogenesis of renal ischemia–reperfusion (I/R) injury. The importance of infiltrating neutrophil, lymphocytes, and macrophage in this kind of injury has been assessed with conflicting results. Annexin 1 is a protein with potent neutrophil anti-migratory activity. In order to evaluate the effects of annexin A1 on renal I/R injury, uninephrectomized rats received annexin A1 mimetic peptide Ac2-26 (100 μg) or vehicle before 30 min of renal artery clamping and were compared to sham surgery animals. Annexin A1 mimetic peptide granted a remarkable protection against I/R injury, preventing glomerular filtration rate and urinary osmolality decreases and acute tubular necrosis development. Annexin A1 infusion aborted neutrophil extravasation and attenuated macrophage infiltration but did not prevent tissue lymphocyte traffic. I/R increased annexin A1 expression (assessed by transmission electron microscopy) in renal epithelial cells, which was attenuated by exogenous annexin A1 infusion. Additionally, annexin A1 reduced I/R injury in isolated proximal tubules suspension. Annexin A1 protein afforded striking functional and structural protection against renal I/R. These results point to an important role of annexin A1 in the epithelial cells defense against I/R injury and indicate that neutrophils are key mediators for the development of tissue injury after renal I/R. If these results were confirmed in clinical studies, annexin A1 might emerge as an important tool to protect against I/R injury in renal transplantation and in vascular surgery.

DOI: 10.1007/s00109-010-0684-4

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@article{Facio2010Annexin1M, title={Annexin 1 mimetic peptide protects against renal ischemia/reperfusion injury in rats}, author={Fernando Nestor Facio and Angela Aparecida Servino Sena and Leandro Pires Ara{\'u}jo and Gl{\'o}ria Elisa Florido Mendes and I. Casanova-Garc{\'i}a de Castro and Marcus Alexandre Mendes Luz and Luis Yu and S{\^o}nia Maria Oliani and Emmanuel de Almeida Burdmann}, journal={Journal of Molecular Medicine}, year={2010}, volume={89}, pages={51-63} }