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Updated: Oct 29, 2025
RNA-seq Analysis of Transcriptomes in Thrombin-treated and Control Human Pulmonary Microvascular Endothelial Cells
Published on: February 13, 2013
miR-19a-3p downregulates tissue factor and functions as a potential therapeutic target for sepsis-induced
Rong Zhang1, Sifen Lu2, Xudan Yang3
1Department of Pediatrics, Sichuan Academy of Medical Sciences&Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, No.32, West section2, 1st ring road, Qingyang District, Chengdu, Sichuan 610072, China.
Abstract:
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. 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 using the chromogenic substrate method. Western blotting was used to detect the protein levels of TF, AKT serine/threonine kinase (AKT), extracellular regulated protein kinases (ERK), nuclear factor kappa B (NF-κB) P65, NFKB inhibitor alpha (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, a human clinical study revealed that miR-19a-3p was downregulated and that TF was upregulated in neonates with sepsis-induced DIC compared with those in the 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-a/IκB-a ratios, and TF procoagulant activity were significantly decreased in lipopolysaccharide (LPS) -induced human peripheral blood mononuclear cells (PBMCs) and human umbilical vein endothelial cells (HUVECs) inhibited by overexpression of miR-19a-3p, and that miR-19a-3p regulating TF was dependent on the NF-kB and AKT pathways. In vivo, miR-19a-3p injection into DIC rats suppressed the mRNA expression of TF; 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 by targeting TF and might be a potential therapeutic target in treating sepsis-induced DIC.
Insights
MicroRNA-19a-3p (miR-19a-3p) may treat sepsis-induced disseminated intravascular coagulation (DIC) by targeting tissue factor (TF). This study found miR-19a-3p downregulation in DIC patients and demonstrated its therapeutic potential in preclinical models.
Area of Science:
- Molecular Biology
- Biochemistry
- Pathology
Background:
- Sepsis-induced disseminated intravascular coagulation (DIC) is a critical condition with high mortality.
- Identifying effective therapeutic targets for DIC is crucial.
Purpose of the Study:
- To investigate the role of microRNA-19a-3p (miR-19a-3p) in sepsis-induced DIC.
- To evaluate miR-19a-3p as a potential therapeutic target by examining its interaction with tissue factor (TF).
Main Methods:
- Bioinformatics and luciferase reporter assays to identify miR-19a-3p targets.
- Quantitative real-time PCR and Western blotting to measure gene and protein expression.
- In vitro cell experiments and in vivo rat models of DIC.
Main Results:
- miR-19a-3p was downregulated, while TF was upregulated in neonates with sepsis-induced DIC.
- TF was confirmed as a direct target of miR-19a-3p.
- Overexpression of miR-19a-3p reduced TF expression, TF procoagulant activity, and inflammatory signaling pathways (NF-κB, AKT) in vitro.
- In vivo, miR-19a-3p administration improved coagulation function and reduced organ damage in a rat DIC model.
Conclusions:
- miR-19a-3p suppresses sepsis-induced DIC by targeting TF.
- miR-19a-3p represents a promising therapeutic candidate for treating DIC.
