MiR-214 represses mitofusin-2 to promote renal tubular apoptosis in ischemic acute kidney injury

Yu Yan, Zhengwei Ma, Jiefu Zhu, Mengru Zeng, Hong Liu, Zheng Dong

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

miR-214 represses mitofusin-2 to promote renal tubular apoptosis in ischemic acute kidney injury. Am J Physiol Renal Physiol 318: F878-F887, 2020. First published January 31, 2020; doi:10.1152/ajprenal. 00567.2019.-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 ATPdepleted 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.

Original languageEnglish (US)
Pages (from-to)F878-F887
JournalAmerican Journal of Physiology - Renal Physiology
Volume318
Issue number4
DOIs
StatePublished - Apr 2020

Keywords

  • Ischemia-reperfusion
  • Kidney
  • Microrna-214
  • Mitochondria
  • Mitofusin

ASJC Scopus subject areas

  • Physiology
  • Urology

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