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Postconditioning attenuates renal ischemia–reperfusion injury by mobilization of stem cells

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Abstract

Background

We recently showed that reactive oxygen species (ROS) and mitochondrial DNA damage and deletions were attenuated by postconditioning (POC). It is not known, however, whether a population of progenitor cells is recruited by POC and is responsible for repair of renal tubular epithelial cells after ischemic injury.

Methods

The model of renal POC was induced by 45 min clamping of the left renal artery and right nephrectomy followed by 7 min of short-time full reperfusion and 3 cycles of 30 s ischemia and 30 s reperfusion. The lymphocyte compartment of peripheral blood was evaluated by fluorescence-activated cell sorting (FACS) to determine expression of the bone marrow-derived progenitor cell markers CXC-chemokine receptor 4 (CXCR4), c-Kit, and CD34, at 12 h, 1 day and 3 days post-ischemia. Serum and kidney tissue were collected for analysis at 3 and 7 days post-ischemia.

Results

Renal functional and structural recovery was markedly improved by POC, which increased the number of CXCR4+ and CD34+ stem cells in peripheral blood and kidney tissue. Inhibition of ROS burst by POC was likely associated with increased hypoxia-inducible factor-1 expression, which may further promote stromal cell-derived factor 1 (SDF-1) expression.

Conclusions

The mechanisms of stem cell recruitment to the injured foci mobilized by POC appear to be mediated by moderate oxidative stress, which may lead to increased SDF-1 expression.

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Acknowledgments

This work was supported by National Natural Science Foundation of China Award number 81470864 and Program of New Century Excellent Talents of Ministry of Education in China, Award number NCET-10-0448.

Conflict of interest

All the authors declare no competing interests.

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Author notes

    Authors and Affiliations

    1. Key Laboratory of Biotechnology and Pharmaceutical Engineering, Molecular Pharmacology Research Center, School of Pharmacy, Wenzhou Medical University, Wenzhou, China

      Xiaohua Tan

    2. Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, You An Men Wai, 100069, Beijing, China

      Ruili Yin & Xiuying Zhang

    3. Department of Pathology, Norman Bethune School of Medicine, Jilin University, Changchun, China

      Yan Chen & Dan Gao

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    1. Xiaohua Tan
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    2. Ruili Yin
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    3. Yan Chen
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    5. Xiuying Zhang
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    Correspondence to Xiuying Zhang.

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    X. Tan and R. Yin contributed equally to this work.

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    Tan, X., Yin, R., Chen, Y. et al. Postconditioning attenuates renal ischemia–reperfusion injury by mobilization of stem cells. J Nephrol 28, 289–298 (2015). https://doi.org/10.1007/s40620-015-0171-7

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