Open Access

Klotho gene delivery ameliorates renal hypertrophy and fibrosis in streptozotocin-induced diabetic rats by suppressing the Rho-associated coiled-coil kinase signaling pathway

  • Authors:
    • Minghong Deng
    • Yumei Luo
    • Yunkui Li
    • Qiuchen Yang
    • Xiaoqin Deng
    • Ping Wu
    • Houxun Ma
  • View Affiliations

  • Published online on: February 17, 2015     https://doi.org/10.3892/mmr.2015.3367
  • Pages: 45-54
  • Copyright: © Deng et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

The present study aimed to investigate whether klotho gene delivery attenuated renal hypertrophy and fibrosis in streptozotocin‑induced diabetic rats. A recombinant adeno‑associated virus (rAAV) carrying mouse klotho full‑length cDNA (rAAV.mKL), was constructed for in vivo investigation of klotho expression. Diabetes was induced in rats by a single tail vein injection of 60 mg/kg streptozotocin. Subsequently, the diabetic rats received an intravenous injection of rAAV.mKL, rAAV.green fluorescent protein (GFP) or phosphate‑buffered saline (PBS). The Sprague‑Dawley rat group received PBS and served as the control group. After 12 weeks, all the rats were sacrificed and ELISA, immunohistochemical and histological analyses, fluorescence microscopy, semi‑quantitative reverse transcription‑polymerase chain reaction and western blottin were performed. A single dose of rAAV.mKL was found to prevent the progression of renal hypertrophy and fibrosis for at least 12 weeks (duration of study). Klotho expression was suppressed in the diabetic rats, but was increased by rAAV.mKL delivery. rAAV.mKL significantly suppressed diabetes‑induced renal hypertrophy and histopathological changes, reduced renal collagen fiber generation and decreased kidney hypertrophy index. In addition, rAAV.mKL decreased the protein expression levels of fibronectin and vimentin, while it downregulated the mRNA expression and activity of Rho‑associated coiled‑coil kinase (ROCK)I in the kidneys of the diabetic rats. These results indicated that klotho gene delivery ameliorated renal hypertrophy and fibrosis in diabetic rats, possibly by suppressing the ROCK signaling pathway. This may offer a novel approach for the long‑term control and renoprotection of diabetes.
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July-2015
Volume 12 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Deng M, Luo Y, Li Y, Yang Q, Deng X, Wu P and Ma H: Klotho gene delivery ameliorates renal hypertrophy and fibrosis in streptozotocin-induced diabetic rats by suppressing the Rho-associated coiled-coil kinase signaling pathway. Mol Med Rep 12: 45-54, 2015.
APA
Deng, M., Luo, Y., Li, Y., Yang, Q., Deng, X., Wu, P., & Ma, H. (2015). Klotho gene delivery ameliorates renal hypertrophy and fibrosis in streptozotocin-induced diabetic rats by suppressing the Rho-associated coiled-coil kinase signaling pathway. Molecular Medicine Reports, 12, 45-54. https://doi.org/10.3892/mmr.2015.3367
MLA
Deng, M., Luo, Y., Li, Y., Yang, Q., Deng, X., Wu, P., Ma, H."Klotho gene delivery ameliorates renal hypertrophy and fibrosis in streptozotocin-induced diabetic rats by suppressing the Rho-associated coiled-coil kinase signaling pathway". Molecular Medicine Reports 12.1 (2015): 45-54.
Chicago
Deng, M., Luo, Y., Li, Y., Yang, Q., Deng, X., Wu, P., Ma, H."Klotho gene delivery ameliorates renal hypertrophy and fibrosis in streptozotocin-induced diabetic rats by suppressing the Rho-associated coiled-coil kinase signaling pathway". Molecular Medicine Reports 12, no. 1 (2015): 45-54. https://doi.org/10.3892/mmr.2015.3367