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Overexpression of histamine H4 receptors in the kidney of diabetic rat

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Abstract

Objective and design

The renal expression of H1 and H2 receptors has previously been demonstrated, while that of the H4 receptor has been poorly investigated, and thus the aim of this research was to investigate the expression of the H4 receptor in the kidney of diabetic rats.

Material or subjects

24 8-week-old male Wistar rats.

Treatment

Diabetes was induced in 12 rats by a single intravenous injection of streptozotocin, and animals were killed 6 weeks later.

Methods

Kidneys were collected and processed for quantitative PCR or immunohistochemical analyses. To ascertain the renal topology of the H4 receptor, colocalization experiments were performed with a series of markers.

Results

H4 receptor is expressed in healthy rats, although at a very low level, and is strongly upregulated in diabetic animals. Immunohistochemical analysis revealed the highest immune-positivity in the medulla. Colocalization experiments revealed a close overlap in expression topology of the H4 receptor and both Tamm–Horsfall glycoprotein and aquaporin 1 was observed.

Conclusions

The results demonstrate, for the first time, that the H4 receptor is expressed in the kidney mainly by resident renal cells of the loop of Henlé and that this receptor is significantly overexpressed in diabetic animals, thus suggesting a possible role in the pathogenesis of diabetes-associated renal disease.

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Acknowledgments

This work was supported by the Royal College of Anaesthesia/BJA, COST Action BM0806 (STSM hosted by the University of Durham) and the University of Turin. We are grateful to Dr Sara Castiglia, Dr Mara Rogazzo and Dr Alice Alfonso (Dipartimento di Scienza e Tecnologia del Farmaco, Università degli Studi di Torino) and Dr Stefania Bruno (Department of Internal Medicine, Centre for Molecular Biotechnology and Centre for Research in Experimental Medicine-CeRMS) for technical assistance. Part of this study was presented at the 41st Annual Meeting of the European Histamine Research Society held jointly with COST Action BM0806, Belfast, Northern Ireland, UK May 2–5 2012, and at the 48th EASD Annual Meeting, Berlin, Germany, October 1–5 2012.

Conflict of interest

None.

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Authors and Affiliations

  1. Dipartmento di Scienza e Tecnologia del Farmaco, Università di Torino, Turin, Italy

    A. C. Rosa, E. Benetti, M. Collino, G. Miglio & R. Fantozzi

  2. Department of Internal Medicine, Centre for Molecular Biotechnology and Centre for Research in Experimental Medicine (CeRMS), Turin, Italy

    C. Grange & G. Camussi

  3. Department of Anatomy, Histology and Forensic Medicine, Section of Histology, University of Florence, Florence, Italy

    A. Pini & D. Bani

  4. School of Biological and Biomedical Sciences and Wolfson Research Institute, Durham University, South Road, Durham, DH1 3LE, UK

    M. A. Katebe & P. L. Chazot

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  1. A. C. Rosa
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  2. C. Grange
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  3. A. Pini
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  4. M. A. Katebe
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  5. E. Benetti
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  6. M. Collino
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  7. G. Miglio
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  8. D. Bani
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  9. G. Camussi
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  10. P. L. Chazot
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  11. R. Fantozzi
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Corresponding author

Correspondence to P. L. Chazot.

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Responsible Editor: Andras Falus.

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Rosa, A.C., Grange, C., Pini, A. et al. Overexpression of histamine H4 receptors in the kidney of diabetic rat. Inflamm. Res. 62, 357–365 (2013). https://doi.org/10.1007/s00011-012-0587-7

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  • DOI: https://doi.org/10.1007/s00011-012-0587-7

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