title: Inhibition of microRNA-30a prevents puromycin aminonucleoside-induced podocytic apoptosis by upregulating the glucocorticoid receptor α.
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.
authors: Graduate School of Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors: Hua
authors: H
authors: Xie
authors: Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors: Hong-Li
authors: HL
authors: Lin
authors: Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors: Nan
authors: N
authors: Wang
authors: Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors: Yan-Ling
authors: YL
authors: Sun
authors: Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors: Yu
authors: Y
authors: Kan
authors: Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors: Hui
authors: H
authors: Guo
authors: Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors: Ji-Lin
authors: JL
authors: Chen
authors: Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China.
authors: Ming
authors: M
authors: Fang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation; D002460:Cell Line; D019295:Computational Biology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D050199:Podocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011692:Puromycin Aminonucleoside / Q000633:toxicity*; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D015854:Up-Regulation
chemical_list: D035683:MicroRNAs; C558180:Mirn100 microRNA, mouse; C534715:Mirn30d microRNA, mouse; D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha; D011692:Puromycin Aminonucleoside