MiR-186-5p Downregulates NAMPT and Functions as a Potential Therapeutic Target for Sepsis-Induced Coagulation Disorders

Abstract

Purpose. Present study is aimed to explore the role of miR-186-5p in sepsis-induced coagulation disorders and molecular mechanisms. Methods. Thirty-four sepsis patients and 34 respiratory infection/pneumonia patients were selected in the present study. Polymicrobial sepsis model was created by cecal ligation and puncture (CLP). The mRNA expression was detected by qRT-PCR. Western blot was utilized to measure protein expression. Thromborel S Reagent was applied to measure the prothrombin time (PT). Platelet count of blood was measured via LH 780. ELISA kits were utilized to evaluate the fibrinogen and PAI-1 concentration. Results. MiR-186-5p expression was lower and nicotinamide phosphoribosyltransferase (NAMPT) mRNA expression was higher in sepsis patients in contrast to control group. Coagulation time was markedly prolonged and platelet count was markedly decreased in CLP mice. In addition, fibrinogen concentration was obviously lower and PAI-1 concentration was obviously higher in CLP mice. MiR-186-5p mimic obviously decreased coagulation time and PAI-1 concentration, while raised platelet count and fibrinogen concentration. Targetscan predicted miR-186-5p might directly regulates NAMPT, and luciferase reporter assay verified this prediction. In addition, miR-186-5p mimic obviously inhibited the mRNA expression of NAMPT. Knockdown of NAMPT improved coagulation dysfunction in sepsis. Overexpression of NAMPT reversed the improvement effect of miR-186-5p on coagulation dysfunction. MiR-186-5p mimic markedly inhibited NF-κB pathway. Conclusion. MiR-186-5p inhibited sepsis-induced coagulation disorders via targeting NAMPT and inactivating NF-κB pathway.

Bioinformatics analysis revealed aging-related diagnostic genes and therapeutic targets in pulmonary arterial hypertension

“…In addition, miR-186-5p has previously been reported as a circulating biomarker of cardiovascular risk, contributing to the diagnosis of acute coronary syndrome [37][38]. MiRNA-186-5p inhibits sepsis induced coagulation disorders by targeting NAMPT and inactivating the NF-κB pathway [39]. Recent studies have con rmed that the upregulation of PVT1 by hypoxia can promote the expression of CTGF, resulting in autophagy disactivation and abnormal proliferation of pulmonary artery smooth muscle cells.…”

Retracted: MiR-186-5p Downregulates NAMPT and Functions as a Potential Therapeutic Target for Sepsis-Induced Coagulation Disorders

“…Computational Intelligence and Neuroscience has retracted the article titled “MiR-186-5p Downregulates NAMPT and Functions as a Potential Therapeutic Target for Sepsis-Induced Coagulation Disorders” [ 1 ] due to concerns that the peer review process has been compromised.…”

“…Computational Intelligence and Neuroscience has retracted the article titled "MiR-186-5p Downregulates NAMPT and Functions as a Potential Terapeutic Target for Sepsis-Induced Coagulation Disorders" [1] due to concerns that the peer review process has been compromised. Following an investigation conducted by the Hindawi Research Integrity team [2], signifcant concerns were identifed with the peer reviewers assigned to this article; the investigation has concluded that the peer review process was compromised.…”