Z Gastroenterol 2014; 52 - KC125
DOI: 10.1055/s-0034-1386427

Modulating liver regeneration by miR-142-3P encapsulated in microparticles

S Kuhn 1, K Splith 1, I Kämmerer 1, C Hegewald 1, L Feldbrügge 1, 2, 3, J Schulte am Esch 4, S Jonas 1, 2, SC Robson 3, M Schmelzle 1, 2, 3
  • 1Translational Centre of Regenerative Medicine (TRM) Leipzig, University of Leipzig, Leipzig, Germany
  • 2Department of Visceral-, Transplantation-, Thoracic- and Vascular Surgery, University Hospital Leipzig, Leipzig, Germany
  • 3The Transplant Institute and Division of Gastroenterology, Beth Israel Deaconess Medical Centre, Harvard University, Boston, United States
  • 4Department of Surgery, University Hospital Düsseldorf, Düsseldorf, Germany

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.