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SaRNA-mediated activation of TRPV5 reduces renal calcium oxalate deposition in rat via decreasing urinary calcium excretion

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Abstract

Hypercalciuria is a main risk factor for kidney stone  formation. TRPV5 is the gatekeeper protein for mediating calcium transport and reabsorption in the kidney. In the present study, we tested the effect of TRPV5 activation with small activating RNA (saRNA), which could induce gene expression by targeting the promoter of the gene, on ethylene glycol (EG)-induced calcium oxalate (CaOx) crystals formation in rat kidney. Five pairs of RNA activation sequences targeting the promoter of rat TRPV5 were designed and synthesized. The synthesized saRNA with the strongest activating effect was selected, and transcellular calcium transportation was tested by Fura-2 analysis. Subsequently, Sprague–Dawley rats were equally divided into three groups and fed with water, 1% EG for 28 days after injecting the negative control saRNA, 1% EG for 28 days after injecting the selected TRPV5-saRNA, respectively. The CaOx crystal formation and the 24-h urine components were assessed. In vitro study, saRNA ds-320 could significantly activate the expression of TRPV5 and transcellular calcium transportation. In vivo study, after 28 days treatment of EG, rats pre-infected with saRNA ds-320 had lower urinary calcium excretion and renal CaOx crystals formation as compared to that pre-infected with negative control saRNA. Activation of TRVP5 with saRNA ds-320 could inhibit EG-induced calcium oxalate crystals formation via promoting urine calcium reabsorption and decreasing urine calcium excretion in rats.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (No. 81370804 and No. 81170652) and the Science and Technology Project in Guangzhou (No. 201604020001).

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Author notes

  1. Tao Zeng, Xiaolu Duan and Wei Zhu contributed equally to this work as the co-first authors.

Authors and Affiliations

  1. Department of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Kangda Road 1#, Haizhu District, Guangzhou, 510230, Guangdong, China

    Tao Zeng, Xiaolu Duan, Wei Zhu, Yang Liu, Wenqi Wu & Guohua Zeng

  2. Guangdong Key Laboratory of Urology, Minimally Invasive Surgery Center, The First Affiliated Hospital of Guangzhou Medical University, Kangda Road 1#, Haizhu District, Guangzhou, 510230, Guangdong, China

    Tao Zeng, Xiaolu Duan, Wei Zhu, Yang Liu, Wenqi Wu & Guohua Zeng

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  1. Tao Zeng
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  2. Xiaolu Duan
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  3. Wei Zhu
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  4. Yang Liu
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  6. Guohua Zeng
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Correspondence to Guohua Zeng.

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The authors of this study disclose no conflicts of interest.

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Zeng, T., Duan, X., Zhu, W. et al. SaRNA-mediated activation of TRPV5 reduces renal calcium oxalate deposition in rat via decreasing urinary calcium excretion. Urolithiasis 46, 271–278 (2018). https://doi.org/10.1007/s00240-017-1004-z

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  • DOI: https://doi.org/10.1007/s00240-017-1004-z

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