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miR‐181c protects CsA‐induced renal damage and fibrosis through inhibiting EMT
Author(s) -
Sun Wenjuan,
Min Binying,
Du Dewei,
Yang Feng,
Meng Junping,
Wang Wen,
Zhao Jie,
Tan Xiaomeng,
Li Zhanting,
Sun Jifeng
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12872
Subject(s) - fibrosis , medicine , urology
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 micro RNA 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.