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DOI: 10.1055/s-0034-1386427
Modulating liver regeneration by miR-142-3P encapsulated in microparticles
Background and aims: Plasma microparticles (MP) have recently been suggested to contain microRNA (miR) and act as novel intercellular carriers. MiR-142 – 3 p is associated with inflammatory responses. We hypothesized that hematopoietic stem cells (HSC) might respond to partial hepatectomy by shedding of CD133+ MP with miR-142 – 3 p MP levels being modulated by ectonucleotidase surface profiles.
Methods: 70% hepatectomy was performed in C57Bl/6 wild type, Cd39 null and Cd73 null mice. MP were purified from the plasma and supernatant by 2-step ultracentrifugation. Total RNA isolated from MP and miR were detected by qPCR. Liver sinusoidal endothelial cells were transfected with miR via lipofection.
Results: MP derived from Cd39 null and Cd73 null mice contain lower levels of miR-142 – 3 p after partial hepatectomy, when compared to wild type mice (p < 0.05). In vitro, miR-142 – 3 p levels in bone marrow mononuclear cell (MNC) derived MP were significantly decreased after stimulation with ATP and ATPγS (p < 0.05) for 4h. This effect was abolished after co-incubation with oxATP, a selective P2X7 receptor antagonist. In contrast, stimulation with adenosine resulted in increased levels of miR-142 – 3 p. Liver endothelial cells showed decreased transcriptional levels of Tnfα and Il1β in response to transfection with miR-142 – 3 p.
Conclusion: Non-coding miR-142 – 3 p is encapsulated in plasma MP with levels being modulated by the hydrolysis of extracellular ATP via CD39 in a P2X7-dependent manner. MP might modulate vascular inflammation dependent on miR-142 – 3 p levels via downregulation of proinflammatory cytokines. These observations have implications for monitoring and indicate future therapeutic avenues in liver regeneration.