miR-181c protects CsA-induced renal damage and fibrosis through inhibiting EMT
| Autor: | Dewei Du, Zhanting Li, Sun Wenjuan, Zhao Jie, Binying Min, Wang Wen, Yang Feng, Xiaomeng Tan, Jifeng Sun, Meng Junping |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Epithelial-Mesenchymal Transition NF-E2-Related Factor 2 Biophysics Biology Kidney Biochemistry Nephrotoxicity Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Structural Biology Fibrosis microRNA Genetics medicine Animals Humans Receptor Notch2 Epithelial–mesenchymal transition Molecular Biology Transcription factor Cell Line Transformed Mice Knockout Microarray analysis techniques Cell Biology medicine.disease MicroRNAs 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Immunology Cyclosporine Cancer research Kidney Diseases |
| Zdroj: | FEBS Letters. 591:3588-3599 |
| ISSN: | 0014-5793 |
| Popis: | Cyclosporine A (CsA), a widely used immunosuppressive drug in organ transplantation and autoimmune disorders, frequently induces renal damage and fibrosis. Recent evidence has implicated epithelial-mesenchymal transition (EMT) in CsA-induced nephrotoxicity. Microarray analysis disclosed miR-181c as the microRNA most dramatically repressed by CsA. Downregulation of miR-181c expression at the transcriptional level by CsA is dependent on the transcription factor Nrf2. miR-181c mimics or inhibitors attenuate or aggravate CsA-induced EMT gene changes, respectively. Importantly, in Nrf2-/- mice, CsA-induced renal damage, fibrosis, and EMT gene changes are restored by miR-181c mimics. Mechanistically, we identified Notch2 as a potential target of miR-181c. Collectively, our data support the notion that miR-181c may serve as an important factor for protecting renal tissues from CsA-induced nephrotoxicity. |
| Databáze: | OpenAIRE |
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