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Article Open Access

Folic acid reverses uric acid crystal-induced surface OAT1 internalization by inhibiting RhoA activity in uric acid nephropathy

  • Authors:
    • Xinlin Wu
    • Jianxiang Liu
    • Jianqing Zhang
    • Heng Liu
    • Miansheng Yan
    • Birong Liang
    • Hongbo Xie
    • Shijun Zhang
    • Baoguo Sun
    • Houming Zhou
  • View Affiliations / Copyright

    Affiliations: Department of Traditional Chinese Medicine, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China, Key Laboratory of Medicinal Biotechnology, Guilin Medical University, Guilin, Guangxi 541004, P.R. China
    Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2385-2392
    |
    Published online on: January 29, 2016
       https://doi.org/10.3892/mmr.2016.4837
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Abstract

To investigate how organic anion transporter (OAT)-1 is involved in uric acid nephropathy (UAN), a rat model for UAN was established and the serum uric acid, blood urea nitrogen and serum creatinine levels were all measured, and observed to be increased. It was additionally identified that in UAN rats the surface OAT1 expression levels were reduced. By treating HEK cells with monosodium urate (MSU) crystals, it was observed that the cells exhibited a reduction in OAT1 levels. Furthermore, MSU crystals were observed to recruit Ras homolog family member A (RhoA), a small guanosine triphosphatase, to the membrane and activate it. Following RhoA activation, the OAT1 internalization rate was identified to be increased. The dominant‑negative RhoA N19 mutation was able to block MSU‑induced OAT1 internalization, indicating that the process was RhoA‑dependent. Finally, the results indicated that folic acid, a daily nutritional supplement, was capable of rescuing MSU‑induced nephropathy and OAT1 internalization. These observations indicated that uric acid crystals were able to reduce the OAT1 membrane distribution through activating RhoA, and that folic acid was capable of preventing MSU-induced OAT1 relocation by inhibiting the RhoA signaling pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Wu X, Liu J, Zhang J, Liu H, Yan M, Liang B, Xie H, Zhang S, Sun B, Zhou H, Zhou H, et al: Folic acid reverses uric acid crystal-induced surface OAT1 internalization by inhibiting RhoA activity in uric acid nephropathy. Mol Med Rep 13: 2385-2392, 2016.
APA
Wu, X., Liu, J., Zhang, J., Liu, H., Yan, M., Liang, B. ... Zhou, H. (2016). Folic acid reverses uric acid crystal-induced surface OAT1 internalization by inhibiting RhoA activity in uric acid nephropathy. Molecular Medicine Reports, 13, 2385-2392. https://doi.org/10.3892/mmr.2016.4837
MLA
Wu, X., Liu, J., Zhang, J., Liu, H., Yan, M., Liang, B., Xie, H., Zhang, S., Sun, B., Zhou, H."Folic acid reverses uric acid crystal-induced surface OAT1 internalization by inhibiting RhoA activity in uric acid nephropathy". Molecular Medicine Reports 13.3 (2016): 2385-2392.
Chicago
Wu, X., Liu, J., Zhang, J., Liu, H., Yan, M., Liang, B., Xie, H., Zhang, S., Sun, B., Zhou, H."Folic acid reverses uric acid crystal-induced surface OAT1 internalization by inhibiting RhoA activity in uric acid nephropathy". Molecular Medicine Reports 13, no. 3 (2016): 2385-2392. https://doi.org/10.3892/mmr.2016.4837
Copy and paste a formatted citation
x
Spandidos Publications style
Wu X, Liu J, Zhang J, Liu H, Yan M, Liang B, Xie H, Zhang S, Sun B, Zhou H, Zhou H, et al: Folic acid reverses uric acid crystal-induced surface OAT1 internalization by inhibiting RhoA activity in uric acid nephropathy. Mol Med Rep 13: 2385-2392, 2016.
APA
Wu, X., Liu, J., Zhang, J., Liu, H., Yan, M., Liang, B. ... Zhou, H. (2016). Folic acid reverses uric acid crystal-induced surface OAT1 internalization by inhibiting RhoA activity in uric acid nephropathy. Molecular Medicine Reports, 13, 2385-2392. https://doi.org/10.3892/mmr.2016.4837
MLA
Wu, X., Liu, J., Zhang, J., Liu, H., Yan, M., Liang, B., Xie, H., Zhang, S., Sun, B., Zhou, H."Folic acid reverses uric acid crystal-induced surface OAT1 internalization by inhibiting RhoA activity in uric acid nephropathy". Molecular Medicine Reports 13.3 (2016): 2385-2392.
Chicago
Wu, X., Liu, J., Zhang, J., Liu, H., Yan, M., Liang, B., Xie, H., Zhang, S., Sun, B., Zhou, H."Folic acid reverses uric acid crystal-induced surface OAT1 internalization by inhibiting RhoA activity in uric acid nephropathy". Molecular Medicine Reports 13, no. 3 (2016): 2385-2392. https://doi.org/10.3892/mmr.2016.4837
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