MicroRNA-494 Promotes Cyclosporine-Induced Nephrotoxicity and Epithelial to Mesenchymal Transition by Inhibiting PTEN
| Autor: | Christopher J. Benway, Jin Yuan, Jessamyn Bagley, John Iacomini |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Male
Epithelial-Mesenchymal Transition Down-Regulation Pharmacology Nephrotoxicity Mice Downregulation and upregulation microRNA medicine Animals Immunology and Allergy PTEN Pharmacology (medical) Epithelial–mesenchymal transition Transplantation Gene knockdown biology business.industry PTEN Phosphohydrolase Epithelial Cells Acute Kidney Injury Epithelium Up-Regulation Mice Inbred C57BL MicroRNAs Kidney Tubules medicine.anatomical_structure Gene Expression Regulation Models Animal Toxicity Cyclosporine biology.protein business |
| Zdroj: | American Journal of Transplantation. 15:1682-1691 |
| ISSN: | 1600-6135 |
| DOI: | 10.1111/ajt.13161 |
| Popis: | A major complication associated with cyclosporine (CsA) treatment is nephrotoxicity. In this study, we examined whether microRNAs play a role in cyclosporine-induced nephrotoxicity. Treatment of mice with CsA resulted in nephrotoxicity that was associated with an early increase in expression of microRNA mmu-miR-494 (miR-494). Similarly, tubular epithelial cell epithelial-mesenchymal transition (EMT) induced by CsA toxicity resulted in the upregulation of microRNA-494 and a decrease in PTEN levels in vitro. miR-494 directly targeted Pten and negatively regulated its expression. Preventing Pten targeting by miR-494 was sufficient to prevent CsA induced EMT. Knockdown of miR-494 prevented the downregulation of PTEN in tubular epithelial cells following CsA treatment and also prevented CsA induced EMT. Thus, miR-494 plays a major role in promoting CsA induced nephrotoxicity through its ability to target Pten thereby contributing to EMT. We suggest that manipulating miR-494 expression may represent a novel approach to preventing EMT associated with CsA induced nephrotoxicity. |
| Databáze: | OpenAIRE |
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