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

Zhang, Rong; Lu, Sifen; Yang, Xiguang; Li, Maojun; Jia, Hui; Liao, Jing; Jing, Qing; Wu, Yanmei; Wang, Haichuan; Xiao, Feng; X, Bai; Na, Xiaoxue; Kang, Yulin; Wan, Ling; Jy, Yang

doi:10.1016/j.bcp.2021.114671

Cited by 15 publications

(7 citation statements)

References 47 publications

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“…These results indicated miR-186-5p improved coagulation dysfunction in sepsis. Some studies have demonstrated that miRNAs are involved in coagulation disorders [ 15 – 17 ]. For instance, miR-19a-3p inhibited disseminated intravascular coagulation induced by sepsis through binding to TF [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

“…Some studies have demonstrated that miRNAs are involved in coagulation disorders [ 15 – 17 ]. For instance, miR-19a-3p inhibited disseminated intravascular coagulation induced by sepsis through binding to TF [ 15 ]. MiR-186-5p affects tumor progression through a variety of ways, including regulating target genes to inhibit cell growth, promoting cell cycle arrest and apoptosis, preventing tumor cell invasion and metastasis, and reducing tumor angiogenesis and lymphangiogenesis [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

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

Shen

Xie

Peng

et al. 2022

Computational Intelligence and Neuroscience

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Shen

Xie

Peng

et al. 2022

Computational Intelligence and Neuroscience

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“…Excessive oxidative stress weakens the scavenging effects of superoxide dismutase and catalase [ 43 ], and impairs the integrity of cell membranes. In drug-dependent patients, oxidative stress will combine with the inflammatory response, promote platelet aggregation in damaged tissue, and aggravate cerebral ischemia and hypoxia, creating a vicious cycle [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

SNP-based and haplotype-based genome-wide association on drug dependence in Han Chinese

Xu,

Kang,

Liang

et al. 2024

BMC Genomics

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Background Drug addiction is a serious problem worldwide and is influenced by genetic factors. The present study aimed to investigate the association between genetics and drug addiction among Han Chinese. Methods A total of 1000 Chinese users of illicit drugs and 9693 healthy controls were enrolled and underwent single nucleotide polymorphism (SNP)-based and haplotype-based association analyses via whole-genome genotyping. Results Both single-SNP and haplotype tests revealed associations between illicit drug use and several immune-related genes in the major histocompatibility complex (MHC) region (SNP association: log10BF = 15.135, p = 1.054e-18; haplotype association: log10BF = 20.925, p = 2.065e-24). These genes may affect the risk of drug addiction via modulation of the neuroimmune system. The single-SNP test exclusively reported genome-wide significant associations between rs3782886 (SNP association: log10BF = 8.726, p = 4.842e-11) in BRAP and rs671 (SNP association: log10BF = 7.406, p = 9.333e-10) in ALDH2 and drug addiction. The haplotype test exclusively reported a genome-wide significant association (haplotype association: log10BF = 7.607, p = 3.342e-11) between a region with allelic heterogeneity on chromosome 22 and drug addiction, which may be involved in the pathway of vitamin B12 transport and metabolism, indicating a causal link between lower vitamin B12 levels and methamphetamine addiction. Conclusions These findings provide new insights into risk-modeling and the prevention and treatment of methamphetamine and heroin dependence, which may further contribute to potential novel therapeutic approaches.

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“…Lower levels of these miRNAs were found in monocytes from SLE and antiphospholipid syndrome patients compared to healthy individuals and inversely correlated with TF mRNA levels [43]. Later, a functional effect of miR-19a-3p on TF was described by Zhang et al [44] in a rat model of sepsis-induced disseminated intravascular coagulation (DIC). These authors verified this regulation in peripheral blood mononuclear cells and HUVECs and deciphered that miR-19a-3p regulation of TF was dependent on the NF-kB and Akt pathways.…”

Section: Monocyte Mirnas As Regulators Of Net Formationmentioning

confidence: 96%

“…These authors verified this regulation in peripheral blood mononuclear cells and HUVECs and deciphered that miR-19a-3p regulation of TF was dependent on the NF-kB and Akt pathways. More interestingly, they observed that miR-19a-3p injection reduced TF expression, coagulation markers, and histopathological indicators of DIC in rat organs [44]. Whether any of these or additional miRNAs [45] have a functional effect in thrombo-inflammatory diseases through direct control of TF remains to be firmly established.…”

Section: Monocyte Mirnas As Regulators Of Net Formationmentioning

confidence: 99%

microRNAs and thrombo-inflammation: relationship in sight

Águila,

González-Conejero,

Martínez

2024

Current Opinion in Hematology

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Purpose of review Thrombo-inflammation is a multifaceted pathologic process involving various cells such as platelets, neutrophils, and monocytes. In recent years, microRNAs have been consistently implicated as regulators of these cells. Recent findings MicroRNAs play a regulatory role in several platelet receptors that have recently been identified as contributing to thrombo-inflammation and neutrophil extracellular trap (NET) formation. In addition, a growing body of evidence has shown that several intracellular and extracellular microRNAs directly promote NET formation. Summary Targeting microRNAs is a promising therapeutic approach to control thrombosis in patients with both infectious and noninfectious inflammatory diseases. Future research efforts should focus on elucidating the specific roles of microRNAs in thrombo-inflammation and translating these findings into tangible benefits for patients.

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

Cited by 15 publications

References 47 publications

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

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

SNP-based and haplotype-based genome-wide association on drug dependence in Han Chinese

microRNAs and thrombo-inflammation: relationship in sight

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