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Expression of SDF-1/CXCR4 in injured human kidneys

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Abstract

The chemokine SDF-1α is involved in migration, survival, and development of multiple cells, most notably of hematopoietic stem cells (HSC) expressing its ligand CXCR4. Recently, we have shown engraftment of human HSC in the ischemically injured murine kidney, presumably mediated by SDF-1α. To further investigate a possible role of SDF-1α in the recruitment of CXCR4+ cells in human renal disease of varying etiologies, we immunostained human biopsies of immunoglobulin (Ig)A nephropathy, minimal-change nephrotic syndrome, focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis, chronic pyelonephritis, and acute tubular necrosis (ATN) for SDF-1α, CXCR4, and CD45, a pan-hematopoietic marker. Irrespective of the diagnosis, intense SDF-1α immunoreactivity was localized to distal tubules and collecting ducts, whereas CXCR4 showed intense staining in both distal and proximal tubules. In addition, whereas varying degrees of CD45+ cell infiltrates were observed in all biopsies, we found focal infiltrates of CXCR4+ cells mostly localized to the corticomedullary junction only in ischemic ATN. This correlated with more extensive staining for SDF-1α in these sites. In all investigated renopathologic conditions, CD45+ leukocyte recruitment to the kidney seems not to be driven by SDF-1α/CXCR4 interaction. A contribution of SDF-1α for influx of CXCR4+ cells in the vicinity of arcuate vessels is suggested only in human ATN.

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Acknowledgements

This study was partially supported by grants from the Israel Scientific Foundation Physician-Scientist Grant Award, Sheba Career Development Award, and Moriss Kahn Career Development Award (BD). We thank Anat Shlosberg for her technical assistance.

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Authors and Affiliations

  1. Department of Pediatric Nephrology, Sackler Faculty of Medicine, Tel Aviv University, Sheba Medical Center, Tel Hashomer, 52621, Israel

    Danny Lotan & Benjamin Dekel

  2. Department of Pediatrics, Sackler Faculty of Medicine, Tel Aviv University, Sheba Medical Center, Tel Hashomer, 52621, Israel

    Natalia Sheinberg & Benjamin Dekel

  3. Department of Pathology, Sackler Faculty of Medicine, Tel Aviv University, Sheba Medical Center, Tel Hashomer, 52621, Israel

    Jury Kopolovic

  4. Laboratory of Regenerative Nephrology, Sackler Faculty of Medicine, Tel Aviv University, Sheba Medical Center, Tel Hashomer, 52621, Israel

    Natalia Sheinberg & Benjamin Dekel

  5. Pediatric Stem Cell Research Institute, Safra Children’s Hospital, Sheba Medical Center, Tel Hashomer, 52621, Israel

    Benjamin Dekel

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  1. Danny Lotan
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  2. Natalia Sheinberg
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  3. Jury Kopolovic
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  4. Benjamin Dekel
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Correspondence to Benjamin Dekel.

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Lotan, D., Sheinberg, N., Kopolovic, J. et al. Expression of SDF-1/CXCR4 in injured human kidneys. Pediatr Nephrol 23, 71–77 (2008). https://doi.org/10.1007/s00467-007-0648-2

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  • DOI: https://doi.org/10.1007/s00467-007-0648-2

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