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

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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.

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Acknowledgments

EA Burdmann and S. M. Oliani are partially supported by grants from Foundation for the Support of Research in the State of São Paulo (Fundação de Amparo à Pesquisa do Estado de São Paulo) and from the National Council for Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico, process 307371/2006-9 and 306074/2007-9, respectively). The authors are grateful to Livia C. Burdmann for the excellent grammar review of the manuscript.

Conflicts of interest

The authors have no competing financial interests to disclose in relation to this manuscript.

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Author notes

  1. Emmanuel A. Burdmann

    Present address: Division of Nephrology, University of São Paulo Medical School, Av. Dr Eneas de Carvalho Aguiar, 255 7º andar—sala 708F, São Paulo, São Paulo, 05403-000, Brazil

Authors and Affiliations

  1. Division of Nephrology, São José do Rio Preto Medical School, Av. Brigadeiro Faria Lima 5416, São José do Rio Preto, São Paulo, 15090-000, Brazil

    Fernando N. Facio Jr, Gloria E. Mendes, Marcus A. M. Luz & Emmanuel A. Burdmann

  2. Department of Biology, Instituto de Biociências Letras e Ciências Exatas (IBILCE), São Paulo State University (UNESP), Rua Cristovão Colombo, 2265, São José do Rio Preto, São Paulo, 15054-000, Brazil

    Angela A. Sena, Leandro P. Araújo & Sonia Maria Oliani

  3. Division of Nephrology, University of São Paulo Medical School, Av. Dr Eneas de Carvalho Aguiar, 255 7º andar—sala 708F, São Paulo, São Paulo, 05403-000, Brazil

    Isac Castro & Luis Yu

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Emmanuel A. Burdmann and Sonia Maria Oliani share senior authorship of this manuscript.

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Facio, F.N., Sena, A.A., Araújo, L.P. et al. Annexin 1 mimetic peptide protects against renal ischemia/reperfusion injury in rats. J Mol Med 89, 51–63 (2011). https://doi.org/10.1007/s00109-010-0684-4

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  • DOI: https://doi.org/10.1007/s00109-010-0684-4

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