miR-29b regulates Ang II-induced EMT of rat renal tubular epithelial cells via targeting PI3K/AKT signaling pathway

Hu,Hongtao; Hu,Shuang; Xu,Shen; Gao,Yue; Zeng,Fang; Shui,Hua

doi:10.3892/ijmm.2018.3579

miR-29b regulates Ang II-induced EMT of rat renal tubular epithelial cells via targeting PI3K/AKT signaling pathway

Authors:
- Hongtao Hu
- Shuang Hu
- Shen Xu
- Yue Gao
- Fang Zeng
- Hua Shui
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Affiliations: Department of Nephrology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China
Published online on: March 22, 2018 https://doi.org/10.3892/ijmm.2018.3579
Pages: 453-460

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Abstract

Renal interstitial fibrosis is a necessary step in the progression of chronic kidney to end stage renal disease. MicroRNA-29 (miR-29) has been shown to play essential roles in epithelial-mesenchymal transition (EMT), and thus may contribute to the regulation of renal interstitial fibrosis. However, the role of miR-29 in the regulation of EMT during chronic kidney disease and renal transplantation has been a source of intense debate, and the mechanisms underlying this process are incompletely understood. In this study, we investigated the function of miR-29b in the regulation of EMT and to gain a better understanding of the mechanism by which miR-29b modulates EMT by targeting the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling pathway during the process of renal interstitial fibrosis. The rat proximal tubular epithelial cell line NRK-52E was cultured in DMEM and treated with angiotensin II (Ang II) at various concentrations. RT-PCR was performed to investigate changes in the levels of expression of miR-29b in NRK-52E cells and western blotting was used to analyze the expression of PI3K, p-AKT, vimentin and keratin 18. The result of the study show that treatment of NRK-52E cells with Ang II induced the transition of the cellular phenotype from epithelial to mesenchymal and upregulated the PI3K/AKT signaling pathway; this was also found following treatment with a phosphatase and tensin homolog on chromosome 10 (PTEN)-specific inhibitor. Increased expression of miR-29b was able to reverse the phenotype induced by Ang II in NRK-52E cells and blocking miR-29b activity with an miR-29b inhibitor resulted in enhanced EMT. Additionally, the PI3K/AKT signaling pathway was found to be suppressed in the presence of enhanced expression of miR-29b by direct binding to 3'-untranslated region (3'-UTR) of PIK3R2. We concluded that miR-29b plays an important role in the negative regulation of Ang II-induced EMT via PI3K/AKT signaling pathway and propose that enhancing miR-29b level or blocking PI3K/AKT signaling pathway may be a novel therapeutic target in renal interstitial fibrosis.

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