Platelet microparticles‐derived miR‐25‐3p promotes the hepatocyte proliferation and cell autophagy via reducing B‐cell translocation gene 2

Abstract

Platelets are critical regulators of liver regeneration, but the mechanisms are still not fully understood. Platelets have been shown to contain a wide variety of microRNAs (miRNAs) and play an important role in many diseases. However, the mechanism that how the platelet microparticles (PMPs)-derived miRNA regulate the hepatocyte proliferation is not very clear. In this study, we have successfully isolated and identified PMPs. We also found that PMPs, which could be well integrated into the HHL-5 cells, could upregulate the level of miR-25-3p in HHL-5 cells. Meanwhile, we found that PMPs-derived miR-25-3p promoted HHL-5 cells proliferation by accelerating cells into the S phase, and enhanced the autophagy by increasing the LC3II expression and reducing the P62 expression. Then, we proved that the miR-25-3p could target the B-cell translocation gene 2 (BTG2) and downregulate the expression levels of the BTG2 gene in HHL-5 cells. In addition, the overexpression of BTG2 significantly inhibited the proliferation and autophagy abilities of HHL-5 cells, while cotransfected miR-25-3p mimics or PMPs could partially rescue HHL-5 cells proliferation and autophagy. Furthermore, we proved that PMPs accelerated hepatocyte proliferation by regulating autophagy pathways. Therefore, PMPs-derived miR-25-3p promoted HHL-5 cell proliferation and autophagy by targeting BTG2, which may be a new therapeutic method for liver regeneration.

Platelet extracellular vesicles and the secretory interactome join forces in health and disease

“…The transfer of miR‐223 from pEVs to peripheral blood mononuclear cells or human coronary artery endothelial cells has also been reported, and led to a decrease in ICAM‐1 expression 95 . Other miRNAs transported by pEVs were shown to affect other cellular targets, such as miR‐142‐3p and miR‐25‐3p, which impact endothelial cells and hepatocytes, respectively 96–98 . Moreover, miRNA's contained in pEVs can affect tumors and impact cancer comorbidities 99,100 .…”

“…95 Other miRNAs transported by pEVs were shown to affect other cellular targets, such as miR-142-3p and miR-25-3p, which impact endothelial cells and hepatocytes, respectively. [96][97][98] Moreover, miRNA's contained in pEVs can affect tumors and impact cancer comorbidities. 99,100 Furthermore, when pEVs were co-incubated with primary macrophages, they efficiently reprogrammed transcription, protein expression, and phagocytic activity of the macrophages, an effect primarily attributed to miRNA, notably miR-16-3p.…”

Platelet, Antiplatelet Therapy and Metabolic Dysfunction-Associated Steatotic Liver Disease: A Narrative Review

“…Moreover, micro-RNA (miRNA) could be transferred from platelets to hepatocytes through the release of microparticles. PMP bearing miR-25-3p induced hepatocyte proliferation by changing gene expression [71].…”

Platelet, Antiplatelet Therapy and Masld: A Narrative Review

“…Moreover, micro-RNA (miRNA) can be transferred from platelets to hepatocytes through the release of microparticles. PMP bearing miR-25-3p induces hepatocyte proliferation by changing gene expression [71].…”