MicroRNA-218 promotes high glucose-induced apoptosis in podocytes by targeting heme oxygenase-1
| Autor: | Haibo Yang, Sutong Li, Qingjun Wang |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Biophysics Down-Regulation Apoptosis p38 Mitogen-Activated Protein Kinases Biochemistry Podocyte Nephrin Diabetic nephropathy Mice 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Animals Humans Diabetic Nephropathies Protein kinase A 3' Untranslated Regions Molecular Biology biology Podocytes Three prime untranslated region Membrane Proteins Cell Biology medicine.disease Up-Regulation Cell biology Enzyme Activation Heme oxygenase MicroRNAs Glucose HEK293 Cells 030104 developmental biology medicine.anatomical_structure Endocrinology Gene Knockdown Techniques 030220 oncology & carcinogenesis biology.protein Glomerular Filtration Barrier Heme Oxygenase-1 |
| Zdroj: | Biochemical and Biophysical Research Communications. 471:582-588 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2016.02.028 |
| Popis: | Emerging evidence has demonstrated that microRNAs (miRNAs) play a mediatory role in the pathogenesis of diabetic nephropathy. In this study, we found that miR-218 was upregulated in high glucose (HG) treated podocytes, which are essential components of the glomerular filtration barrier and a major prognostic determinant in diabetic nephropathy. Additionally, up-regulation of miR-218 was accompanied by an increased rate of podocyte death and down-regulation in the level of nephrin, a key marker of podocytes. However, inhibition of miR-218 exerted the opposite effect. In addition, the dual-luciferase reporter assay showed that miR-218 directly targeted the 3'-untranslated region of heme oxygenase-1 (HO-1), and further study confirmed an increase of HO-1 in HG-treated podocytes transfected with anti-miR-218. Knockdown of HO-1 blocked the anti-apoptotic effect of anti-miR-218. Furthermore, inhibition of miR-218 was associated with decreased expression of the known pro-apoptotic molecule p38-mitogen-activated protein kinase (p38-MAPK) activation. Following preconditioning with SB203580, an inhibitor of p38-MAPK, the stimulatory effect of HG on podocyte apoptosis was strikingly ameliorated. These findings suggested that miR-218 accelerated HG-induced podocyte apoptosis through directly down-regulating HO-1 and facilitating p38-MAPK activation. |
| Databáze: | OpenAIRE |
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