microRNA in Rat Liver Sinusoidal Endothelial Cells and Hepatocytes and Application to Circulating Biomarkers that Discern Pathogenesis of Liver Injuries.

Sinusoidal obstruction syndrome is a serious liver injury caused by toxic injury to liver sinusoidal endothelial cells (LSECs) during clinical chemotherapy. Although circulating microRNAs (miRNAs), such as hepatocyte-specific miR-122-5p and miR-192-5p, have been proposed as potential noninvasive biomarkers of hepatocellular liver injury, these miRNAs may not be specific to damage to other hepatic cell types, including LSECs. Here, we characterized miRNA expression in LSECs and hepatocytes and investigated whether cell type-specific miRNAs in plasma can discern pathogenesis of liver injuries in rats. Comprehensive miRNA expression analyses showed that 66 and 12 miRNAs were highly expressed in LSECs and hepatocytes isolated from non-treated rats, respectively. An LSEC-enriched miR-511-3p was relatively liver specific according to public data. For establishing LSEC and hepatocyte injury models, rats were orally treated with monocrotaline and thioacetamide, respectively. In monocrotaline-treated rats, a sinusoidal obstruction syndrome model, LSEC damage was observed from 6 h after dosing, whereas hepatocellular damage was observed after 48 h. Interestingly, the level of miR-511-3p in plasma was increased as early as 6 h after monocrotaline dosing, followed by an increase of miR-122-5p after 24 h. In the thioacetamide-induced hepatocellular injury model, the level of miR-511-3p was not altered in plasma, whereas miR-122-5p levels were increased after 6 h. In conclusion, we identified miR-511-3p in plasma as a possible biomarker for LSEC damage.