| First Author | Yan Y | Year | 2020 |
| Journal | Am J Physiol Renal Physiol | Volume | 318 |
| Issue | 4 | Pages | F878-F887 |
| PubMed ID | 32003595 | Mgi Jnum | J:294121 |
| Mgi Id | MGI:6451379 | Doi | 10.1152/ajprenal.00567.2019 |
| Citation | Yan Y, et al. (2020) miR-214 represses mitofusin-2 to promote renal tubular apoptosis in ischemic acute kidney injury. Am J Physiol Renal Physiol 318(4):F878-F887 |
| abstractText | Disruption of mitochondrial dynamics is an important pathogenic event in both acute and chronic kidney diseases, but the underlying mechanism remains poorly understood. Here, we report the regulation of mitofusin-2 (Mfn2; a key mitochondrial fusion protein) by microRNA-214 (miR-214) in renal ischemia-reperfusion that contributes to mitochondrial fragmentation, renal tubular cell death, and ischemic acute kidney injury (AKI). miR-214 was induced, whereas Mfn2 expression was decreased, in mouse ischemic AKI and cultured rat kidney proximal tubular cells (RPTCs) following ATP depletion treatment. Overexpression of miR-214 decreased Mfn2. Conversely, inhibition of miR-214 with anti-miR-214 prevented Mfn2 downregulation in RPTCs following ATP depletion. Anti-miR-214 further ameliorated mitochondrial fragmentation and apoptosis, whereas overexpression of miR-214 increased apoptosis, in ATP-depleted RPTCs. To test regulation in vivo, we established a mouse model with miR-214 specifically deleted from kidney proximal tubular cells (PT-miR-214(-/-)). Compared with wild-type mice, PT-miR-214(-/-) mice had less severe tissue damage, fewer apoptotic cells, and better renal function after ischemic AKI. miR-214 induction in ischemic AKI was suppressed in PT-miR-214(-/-) mice, accompanied by partial preservation of Mfn2 in kidneys. These results unveil the miR-214/Mfn2 axis that contributes to the disruption of mitochondrial dynamics and tubular cell death in ischemic AKI, offering new therapeutic targets. |
