Description
In acute kidney injury (AKI) regions of the kidney are hypoxic. However, for reasons yet unknown, adaptation to hypoxia through hypoxia inducible factor (HIF) is limited. Here we seek for potential HIF repressors, their amenability to intervention, and assess the consequences for AKI outcome; Renal miR-22 is up-regulated in AKI. In vitro, miR-22 is inducible by hypoxia, represses HIF, and this repression is offset by specific anti-miR-22 molecules. Inhibition of miR-22 in AKI leads to a complex regulation of more than 3,000 renal genes, most of which are unrelated to the HIF pathway.
Overall Design
Anti-miR-22 (I-mmu-miR-22-3p, sequence 5-3 CTTCAACTGGCAGCT, Exiqon, Denmark) or mock molecules (I-mmu-miR-22-3p MM, sequence 5-3 CTACTACAGGCTGCT, Exiqon, Denmark) were dissolved in 0.9% saline, and injected SC at a dose of 20 mg/kg of body weight 24 h prior to glycerol injection. 50% glycerol injection into the gastrocnemic muscle causes rhabdomyolysis and subsequently acute kidney injury (AKI). 24 h after glycerol injection, animals were euthanized by cervical dislocation under isoflurane narcosis, and kidneys were rapidly removed, halved, and snap frozen in liquid nitrogen
Curator
hy_li