Pituitary-derived small extracellular vesicles promote liver repair by its cargo miR-143-3p.

The small Extracellular vesicles (sEV) has been recognized to be significant for intercellular communication due to their ability to transfer important cellular cargoes like miRNAs through circulation. The pituitary gland has not been clearly known about the role of its secreted sEV under normal physiological conditions. And Liver disease is a global public health burden. The present study is the first to investigate the effect of pituitary sEV on the liver. Sequencing and qRT-PCR revealed miR-143-3p is one of the richest in the pituitary sEV. MiR-143 Knockout (KO) mice resulted in a remarkable decrease in insulin-like growth factor 1 (IGF-1) levels and a significant increase in insulin-like growth factor binding protein 5 (IGFBP5) levels along with a reduction in liver primary cell growth. More importantly, compared with miR-143-KO-sEV, WT-sEV possesses a more robust capacity to improve miR-143 KO mice liver repair through the Wnt/β-catenin pathway after an acute injury caused by carbon tetrachloride (CCl). Our results indicate that pituitary-derived sEV promotes hepatocyte proliferation and liver repair by its cargo miR-143-3p and provides new insight into the regulation mechanism of the pituitary-liver axis, and open a new window for endocrine regulation by using sEV.