miR-19a-3p downregulates tissue factor and functions as a potential therapeutic target for sepsis-induced disseminated intravascular coagulation.

Sepsis-induced disseminated intravascular coagulation (DIC) is a common life-threatening terminal-stage disease with high mortality. This study aimed to identify effective miRNAs as therapeutic targets for DIC.In the present study, bioinformatics and luciferase reporter gene analyses were performed to predict miR-19a-3p and validate that it targets tissue factor (TF). Quantitative real-time PCR was used to detect the expression of miR-19a-3p and TF, and TF procoagulant activity was determined by chromogenic substrate method.Western blotting was used to detect the protein levels of TF, AKT, Erk1/2, NF-κB P65, IκB-a and their phosphorylated counterparts in cell experiments. Furthermore, a rat model was established to explore the potential of miR-19a-3p in DIC treatment. As a result, the human clinical study revealed that miR-19a-3p was downregulated and that TF was upregulated in neonates with sepsis-induced DIC compared with control group. The luciferase reporter assay showed that TF was a direct target of miR-19a-3p. Cell experiments verified that the mRNA and protein levels of TF, and the p-AKT/AKT, p-Erk/Erk, p-P65/P65, p-IκB/IκB-a ratios, and TF procoagulant activity were significantly decreased in lipopolysaccharide-induced human peripheral blood mononuclear cells and human umbilical vein endothelial cells inhibiting by overexpression of miR-19a-3p. miR-19a-3p regulating TF involved with NF-kB pathway and ATK pathway. In vivo, miR-19a-3p injection into DIC rats suppressed the mRNA of TF, and More importantly, significant improvements in coagulation function indicators and in histopathologies of lung and kidney were observed.In conclusion, miR-19a-3p may suppress DIC via targeting TF and might be a potential therapeutic target in treating sepsis-induced DIC.