Inhibition of microRNA‑30a prevents puromycin aminonucleoside‑induced podocytic apoptosis by upregulating the glucocorticoid receptor α

Xie,Hua; Lin,Hong‑Li; Wang,Nan; Sun,Yan‑Ling; Kan,Yu; Guo,Hui; Chen,Ji‑Lin; Fang,Ming

doi:10.3892/mmr.2015.4226

Inhibition of microRNA‑30a prevents puromycin aminonucleoside‑induced podocytic apoptosis by upregulating the glucocorticoid receptor α

Authors:
- Hua Xie
- Hong‑Li Lin
- Nan Wang
- Yan‑Ling Sun
- Yu Kan
- Hui Guo
- Ji‑Lin Chen
- Ming Fang
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Affiliations: Graduate School of Dalian Medical University, Dalian, Liaoning 116044, P.R. China, Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China
Published online on: August 14, 2015 https://doi.org/10.3892/mmr.2015.4226
Pages: 6043-6052

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Abstract

It is well‑established that steroid‑resistant nephrotic syndrome commonly involves podocytic injury, however, the underlying mechanism remains to be elucidated. Previous studies have demonstrated that glucocorticoids enhance podocytic recovery predominantly through the functional isoform, glucocorticoid receptor (GR)α. Our previous study demonstrated the reduced expression of GRα in podocytes from patients with steroid‑resistant nephrotic syndrome compared with those with steroid‑sensitive syndromes, which suggested that microRNAs (miRNAs) may be a potential therapeutic target in the modulation of steroid sensitivity. The present study screened miRNAs in murine injured podocytes by microarray and identified 10 miRNAs significantly upregulated, including miR‑30a, miR‑30d, miR‑100, miR181c, miR‑5099, miR‑3535, miR‑140‑3p, miR‑148‑3p and miR‑103‑3p. Bioinformatic target prediction indicated that the GR was a candidate target gene of miR‑30a. The data also indicated that miR‑30a negatively regulated GRα in normal and injured podocytes induced by puromycin aminonucleoside (PAN). In addition, the inhibition of miR‑30a prevented podocytic apoptosis induced by PAN. However, luciferase reporter assay data suggested an indirect effect on the transcriptional activity of GRα. The present study indicated that silencing of miR‑30a may improve steroid sensitivity in injured podocytes, although the mechanism cannot be explained by conventional means and remains to be elucidated.

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