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Neutrophil gelatinase-associated lipocalin protects renal tubular epithelial cells in hypoxia–reperfusion by reducing apoptosis

  • Nephrology - Original Paper
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Abstract

Purpose

The aim of this study was to elucidate the role of neutrophil gelatinase-associated lipocalin (NGAL) in regulating apoptosis of tubular epithelial cells in a hypoxia–reperfusion model.

Methods

A hypoxia–reperfusion model was established with NRK-52E cells to assess apoptosis and cell cycle progression after the addition of NGAL. We investigated the expression of four apoptosis factors, Bcl-2, Bax, Fas and FasL, as well as the expression level of two NGAL receptors, 24p3R and megalin, by both Western blot and real-time PCR.

Results

NGAL induced cell proliferation and reduced apoptosis by regulating four apoptosis factors Bcl-2, Bax, Fas and FasL. Western blot demonstrated that the two NGAL receptors, 24p3R and megalin, were increased after hypoxia–reperfusion, which was reduced by exogenous NGAL. Moreover, overexpression of the two receptors induced the expression of the anti-apoptotic factor Bcl-2 and reduced the expression of pro-apoptotic Bax, Fas and FasL.

Conclusions

These findings indicate that NGAL reduces apoptosis by regulating the four apoptosis factors Bcl-2, Bax, Fas and FasL through its two receptors 24p3R and megalin. These results also suggest that ectopic expression of NGAL in renal cells might provide a therapeutic strategy in ischemia–reperfusion by reducing apoptosis and promoting renal cell proliferation.

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Acknowledgments

This work was supported by a Shanghai Municipal Health Bureau, bureau-level research project Grant (No. 20114331) and the Advanced Medical Cooperation Project of Songjiang Health Bureau of Shanghai (2011).

Conflict of interest

The authors declare no competing financial interest.

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Authors and Affiliations

  1. Department of Nephrology, Songjiang Hospital Affiliated to the First People´s Hospital of Shanghai Jiaotong University, 746 Songjiang Zhongshan Road, Shanghai, 201600, China

    Xiujuan Zang, Feng Zheng, Hai-juan Hong, Yan Jiang, Ying Song & Yanping Xia

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  1. Xiujuan Zang
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  2. Feng Zheng
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  4. Yan Jiang
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Correspondence to Xiujuan Zang.

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Zang, X., Zheng, F., Hong, Hj. et al. Neutrophil gelatinase-associated lipocalin protects renal tubular epithelial cells in hypoxia–reperfusion by reducing apoptosis. Int Urol Nephrol 46, 1673–1679 (2014). https://doi.org/10.1007/s11255-014-0749-3

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  • DOI: https://doi.org/10.1007/s11255-014-0749-3

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