Time Dependent Distribution of MicroRNA 144 after Intravenous Delivery

Author(s): Jing Li, Sean Cai, Jenny Peng, Mark K. Friedberg, Andrew N. Redington.

Journal Name: MicroRNA

Volume 5 , Issue 1 , 2016

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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.

Keywords: Ago2, Cy3-labelled-miR-144, miR-144 distribution, miR-144, time course.

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Article Details

VOLUME: 5
ISSUE: 1
Year: 2016
Page: [36 - 49]
Pages: 14
DOI: 10.2174/2211536605666160322152146

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