Author:
Zhu Ran,Qi Wei-yi,Liu Ting-wei,Liu Fan
Abstract
Acute pulmonary embolism (APE) is a disabling diseases with high incidence rate and mortality rate. Although with high specificity, D-Dimer lacks specificity to assess APE, hence additional diagnostic and prognostic biomarkers are necessary. APE is widely treated with serine protease urokinase or urokinase-type plasminogen activator (uPA), which act as a catalyst for conversion of plasminogen to plasmin to resolve blood clots. However, it is unknown the role of differential expression of microRNAs (miRNAs) in protective effect of uPA against APE. Hence, we performed miRNA profiling in a hypoxia/reoxygenation (H/R) model of bronchial epithelial BEAS-2B cells in vitro and a APE mice model in vivo. Our analysis revealed that miR-34a-5p, miR-324-5p, miR-331-3p are upregulated with H/R or APE induction, whereas miR-429, miR-491-5p, and miR-449a are downregulated. The differential expression of the miRNAs was attenuated to levels comparable to control by treatment with uPA both in vitro and in vivo. In situ target prediction and analysis of potential functions of the target genes showed that the enrichment of biological processes and pathways were related to cell growth, proliferation, and inflammation. Ectopic overexpression of miR-449a using a mimic completely attenuated the protective effect of uPA in the H/R model in vitro. These results provide a group of miRNAs that could be used as markers, and the modulation of these miRNAs might have potential therapeutic benefits in patients with APE, which need to be validated in additional studies in humans.
Subject
Pharmacology (medical),Pharmacology
Reference46 articles.
1. Predicting Effective microRNA Target Sites in Mammalian mRNAs;Agarwal;Elife,2015
2. MicroRNAs as Biomarkers in Rheumatic Diseases;Alevizos;Nat. Rev. Rheumatol.,2010
3. Chemokines and Atherosclerosis: Focus on the CX3CL1/CX3CR1 Pathway;Apostolakis;Acta Pharmacol. Sin,2013
4. Urokinase Mediates Fibrinolysis in the Pulmonary Microvasculature;Bdeir;Blood,2000
5. Multicenter Clinical Trial on the Efficacy of Thrombolytic Therapy with Urokinase And/or Anticoagulant with Low Molecular Weight Heparin in Acute Pulmonary Embolism;Cheng;Zhonghua Nei Ke Za Zhi,2002
Cited by
2 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献