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The wnt/β-catenin signaling pathway participates in rhein ameliorating kidney injury in DN mice

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Abstract

The present study aimed to investigate the relationship between wnt/β-catenin signaling pathway and kidney impairment in diabetic nephropathy (DN) mice as well as the renoprotective effect of rhein (RH). Mice were randomly divided into four groups (n = 6): db/db mice treated with RH (DN + RH), db/db mice (DN), db/m mice treated with RH (NC + RH) and db/m mice (NC). RH-treated groups were administered orally at a daily dose 120 mg/kg. Mice were sacrificed after 12 weeks of treatments. In our study, increased albuminuria, together with weight gain and hyperglycemia was observed in the beginning of the study and continued to increase throughout the length of the study (12 weeks). Histopathologic changes were observed in the DN group. Expectedly, mice receiving the treatment with RH were protected from this injury. Meanwhile, the expression of nephrin, a podocyte-specific marker, was significantly reduced while wnt1, p-GSK-3β/tGSK-3β, p-β-catenin/tβ-catenin were higher in the DN group mice when analyzed by immunofluorescence and Western blotting. RH reversed these above changes. wnt/β-catenin signaling pathway participates in RH ameliorating kidney injury in DN mice. The manipulation of RH might act as a promising therapeutic intervention for DN.

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Abbreviations

DN:

Diabetic nephropathy

NC:

Normal control

ESRD:

End-stage renal disease

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Acknowledgments

We thank Dr. Zhihong Liu in Jinling Hospital for providing rhein in this study, and the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions. This work was supported by grants from the National Natural Science Foundation of China (81170660/H0509,81370815/H0509, to Changying Xing; 81100512/H0510, to Bo Zhang; 81300573, to Yuanyang Gang), the Ph.D. Programs Foundation of the Ministry of Education of China (2011BAI10B06, 2011BAI10B08, to Changying Xing), the Natural Science Foundation of Jiangsu (LJ201125, BK20151588, BL2012032, BL2014080, to Changying Xing; BK20131030, to Yuanyang Gang).

Authors Contribution

Suyan Duan designed the study and drafted the paper. Bo Zhang was involved in revising the paper. Suyan Duan, Yingyi Wu, Chuanyan Zhao and Yuming Chen carried out the full experiment. Yanggang Yuan and Changying Xing were responsible for study oversight, data collection, analysis. All authors have read the final paper and approved the submission.

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Authors and Affiliations

  1. Department of Nephrology, The First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital), Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, China

    Suyan Duan, Chuanyan Zhao, Mingyu Chen, Yanggang Yuan, Changying Xing & Bo Zhang

  2. Department of Rheumatology, The Wuxi 4th People’s Hospital (The Affiliated Hospital of Jiangnan University), 200 Huihe Road, Wuxi, 214062, Jiangsu, China

    Yingyi Wu

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  1. Suyan Duan
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  2. Yingyi Wu
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  6. Changying Xing
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  7. Bo Zhang
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Correspondence to Bo Zhang.

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Duan, S., Wu, Y., Zhao, C. et al. The wnt/β-catenin signaling pathway participates in rhein ameliorating kidney injury in DN mice. Mol Cell Biochem 411, 73–82 (2016). https://doi.org/10.1007/s11010-015-2569-x

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