Mononuclear-cell-derived microparticles attenuate endothelial inflammation by transfer of miR-142-3p in a CD39...

Area of Science:

• Molecular Biology
• Immunology
• Cell Biology
• Vascular Biology

Background:

• Plasma microparticles (MPs) possess ectonucleotidases of the CD39 family, influencing vascular inflammation.
• MPs can fuse with cells, facilitating the transfer of genetic material, including microRNAs (miRs).
• The role of CD39 and purinergic signaling in modulating MPs' immunomodulatory cargo remains incompletely understood.

Purpose of the Study:

• To investigate if CD39 influences levels of immunomodulatory miRs in plasma MPs post-hepatectomy.
• To determine if purinergic signaling regulates the horizontal transfer of miR-142-3p between mononuclear cells (MNCs) and endothelial cells via MPs.
• To assess the functional consequences of miR-142-3p transfer on endothelial inflammation and apoptosis.

Main Methods:

• Experimental partial hepatectomy was performed in wild-type and CD39-deficient mice.
• Plasma MPs were isolated using ultracentrifugation.
• MNCs were stimulated in vitro with nucleotides/nucleosides; miR-142-3p levels in MPs were quantified.
• Cell-cell fusion and miR-142-3p transfer were visualized using flow cytometry and confocal microscopy.
• Endothelial inflammation and apoptosis were assessed after miR-142-3p transfection.

Main Results:

• CD39-deficient mice exhibited significantly lower miR-142-3p levels in plasma MPs after hepatectomy compared to wild-type controls.
• In vitro, adenosine, but not extracellular nucleotides, significantly increased miR-142-3p levels in MNC-derived MPs.
• MNC-derived MPs effectively transferred miR-142-3p to endothelial cells via fusion.
• Transfection with miR-142-3p reduced TNF-α levels and endothelial apoptosis.

Conclusions:

• CD39 modulates miR-142-3p levels in plasma MPs following hepatectomy, suggesting a role in compensatory vascular responses.
• Purinergic signaling, particularly adenosine, regulates miR-142-3p loading into MPs, indicating a mechanism for intercellular communication.
• The horizontal transfer of miR-142-3p via MPs represents a potential pathway influencing organ regeneration and vascular inflammation.