Title:Time Dependent Distribution of MicroRNA 144 after Intravenous Delivery
Volume: 5
Issue: 1
Author(s): Jing Li, Sean Cai, Jenny Peng, Mark K. Friedberg and Andrew N. Redington
Affiliation:
Keywords:
Ago2, Cy3-labelled-miR-144, miR-144 distribution, miR-144, time course.
Abstract: Background: miR-144 has potential benefits in protecting against myocardial
ischemia and suppression of tumor growth. We have previously shown that a
single intravenous injection of miR-144 provides potent cardioprotection, but its kinetics
and distribution are not known.
Methods: Single stranded mature miR-144 or Cy3-labelled-miR-144 was delivered
into C57/B6 mice by tail vein injection.
Results: After intravenous injection, the signal of Cy3-labelled-miR-144 in the kidney,
brain, heart and liver peaks at 60 minutes, and is predominantly localised to the
endothelium at that stage. In the kidney and heart, Cy3-labelled-miR-144 signal is
detectable within the parenchymal tissues for at least 3 days, after which it starts to
decrease, but brain Cy3-miR-144 signal rapidly decreases after 1 hour, and is lost at day 1, with no parenchymal
uptake detected. Cy3-miR-144 signal can be detected until day 28 in the liver. Stem loop RTPCR
confirmed the temporal pattern shown by miR-144 in kidney, brain and heart, but in liver there
was a continuous rise following the initial injection until day 28 with no signs of decrease, suggesting
de-novo synthesis.
Conclusion: There is early endothelial uptake of injected miR-144 followed by organ-specific distribution
and kinetics. In the liver, there appears to be a positive feedback process that leads to continued accumulation
of miR-144 that persists for at least 28 days. These observations should be taken into account
when designing experiments utilizing parenteral miR-144 and assessing the biology of its actions.
