Overexpression of miR-451a in sepsis and septic shock patients is involved in the regulation of sepsis-associated cardiac dysfunction and inflammation

Wang, Heng; Cui, Wenjuan; Qiao, Lujun; Hu, Guoxin

doi:10.1590/1678-4685-gmb-2020-0009

Cited by 11 publications

(13 citation statements)

References 40 publications

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“…Uncontrolled inflammatory response and refractory immune dysfunction are the main reasons addressing the progression of sepsis. 16 Pathogen culture is often used to diagnose or evaluate the prognosis of sepsis, but its false positive is high and the diagnostic efficiency is undesirable. 17 It has been found that many kinds of lncRNAs are involved in the regulation of inflammation and the immune process, which can be used in the discrimination of sepsis.…”

Section: Discussionmentioning

confidence: 99%

Clinical Significance of the Serum lncRNA NORAD Expression in Patients with Neonatal Sepsis and Its Association with miR-410-3p

Zhang

2021

JIR

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Purpose Neonatal sepsis (NS) is one of the most crucial causes of death in newborns. This investigation aimed to validate the expression level of NORAD and the probable mechanism underlying the function of NORAD in NS. Patients and Methods The expression of NORAD and miR-410-3p was identified by qRT-PCR. The diagnostic sensitivity and specificity of NORAD were examined by the ROC curve. The NS cell models were established by the treatment of lipopolysaccharide (LPS) in the macrophage RAW264.7 cells. The luciferase report assay was performed to detect the target relationship between NORAD and miR-410-3p and the association between them was revealed by Pearson correlation. Results The expression of NORAD was at a higher level in the NS group than in the pneumonia controls. The levels of NORAD could sever as a diagnostic marker on discriminating NS patients from pneumonia neonates. The expression of IL-6, IL-8, and TNF-α was enhanced in the macrophage cells under LPS circumstances, while NORAD knockdown reversed the overexpression of these pro-inflammatory cytokines. Besides, miR-410-3p was a possible ceRNA of NORAD by the finding that the luciferase activity fell in the co-transfection of miR-410-3p mimics and WT-NORAD group. In vitro, LPS management could inhibit the expression of miR-410-3p, while silenced NORAD ameliorated the suppressed miR-410-3p levels. Decreased expression of miR-410-3p was discovered in NS patients and the changes of miR-410-3p expression were correlated with the levels of NORAD in the NS patients. Conclusion We found a raised level of NORAD in the NS patients and it might be a diagnostic indicator for NS patients. NORAD elimination meliorated the inflammation actions steered by LPS. MiR-410-3p was a target of NORAD and lowly expressed in the NS patients.

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Section: Discussionmentioning

confidence: 99%

Clinical Significance of the Serum lncRNA NORAD Expression in Patients with Neonatal Sepsis and Its Association with miR-410-3p

Zhang

2021

JIR

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“…The Sprague-Dawley (SD) model of sepsis was constructed with cecal ligation and puncture (CLP) [ 16 ]. Male SD rats of 8–10 weeks old and weighing 250~300 g of clean grade were purchased from JKbiot (Nanjing, China).…”

Section: Methodsmentioning

confidence: 99%

“…After anesthesia, rats were subjected to tracheostomy and mechanical ventilation. The PowerLab data analysis and processing system were connected, and the catheter was inserted into the left ventricle to measure the left ventricular systolic pressure (LVSP) left ventricular end-diastolic pressure (LVEDP), maximum rate of increase of left ventricular internal pressure (+dp/dtmax), maximum rate of decrease of left ventricular internal pressure (-dp/dtmax), the left ventricular mass (LVM), and left ventricular wall thickness (LVWT) [ 16 , 17 ]. After that, the blood was extracted for the following tests.…”

Section: Methodsmentioning

confidence: 99%

MicroRNA-381-3p signatures as a diagnostic marker in patients with sepsis and modulates sepsis-steered cardiac damage and inflammation by binding HMGB1

et al. 2021

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Immune response imbalance and cardiac dysfunction caused by sepsis are the main reasons for death in sepsis. This study aimed to confirm the expression and diagnostic possibility of microRNA-381-3p (miR-381-3p) and its mechanism in sepsis. Quantitative real-time PCR (qRT-PCR) and receiver operating characteristic (ROC) were used to reveal the levels and clinical significance of miR-381-3p. Pearson correlation was conducted to provide the correlations between miR-381-3p and several indexes of sepsis. The H9c2 cell models were constructed by lipopolysaccharide (LPS), and cecal ligation and puncture (CLP) was applied to establish the Sprague-Dawley (SD) rat models. Cell Counting Kit-8 (CCK-8) and flow cytometry were the methods to detect the cell viability and death rate of H9c2. Enzyme-linked immunosorbent assay (ELISA) was performed to evaluate the concentration of inflammatory cytokines. The target gene of miR-381-3p was validated via the luciferase report system. The low expression of miR-381-3p was found in the serum of patients with sepsis. The lessened miR-381-3p could be a marker in the discrimination of sepsis patients. Overexpression of miR-381-3p could repress the mRNA expression of HMGB1, inhibit the cell apoptosis and inflammatory response, and motivate the viability of sepsis cells. At the same time, enhanced miR-381-3p promoted the inhibition of inflammation and cardiac dysfunction in the rat model of sepsis. Collectively, reduced levels of serum miR-381-3p can be used as an index to detect sepsis patients. MiR-381-3p restored the inflammatory response and myocardial dysfunction caused by sepsis via HMGB1.

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“…MicroRNA-451a (miR-451a), as one of the recently identified microRNAs, is reported to be dysregulated in patients with sepsis, also exhibits close involvement in regulating T cell differentiation and infection-related inflammatory responses ( Cheng et al, 2017 ; Ahmad et al, 2020 ; Liu et al, 2020 ; Wang et al, 2020 ). A recent genomic study has displayed that miR-451a is one of the upregulated differentially expressed genes (DEG) in septic mice ( Ahmad et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, one in vitro experiment exhibits that miR-451a promotes the differentiation of CD4 + T cells into T helper (Th) cells in systemic lupus erythematosus (SLE) ( Cheng et al, 2017 ). Furthermore, miR-451a is reported to upregulate the inflammatory cytokines [such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in septic rats ( Wang et al, 2020 )]. While few clinical studies explore the value of miR-451a measurement in patients with sepsis.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-451a and Th1/Th2 ratio inform inflammation, septic organ injury, and mortality risk in sepsis patients

Geng

Liu

2022

Front. Microbiol.

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AimsMicroRNA-451a (miR-451a) regulates Th1/Th2 cell differentiation, inflammation, and septic organ injury in several experiments. Therefore, the present study aimed to explore the inter-correlation of miR-451a with the Th1/Th2 ratio, and their association with inflammation, septic organ injury, and mortality risk in patients with sepsis.MethodsConsecutively, 117 patients with sepsis and 50 healthy controls (HCs) were enrolled. Peripheral blood mononuclear cell samples were collected to detect miR-451a expression and the Th1/Th2 ratio in all subjects.ResultsMiR-451a (p < 0.001), Th1 cells (p = 0.014), and the Th1/Th2 ratio (p < 0.001) increased, while Th2 cells (p < 0.001) declined in patients with sepsis compared with HCs. It was of note that miR-451a was positively correlated with Th1 cells (p = 0.002) and the Th1/Th2 ratio (p = 0.001), while it was negatively related to Th2 cells (p = 0.005) in patients with sepsis. Meanwhile, miR-451a and the Th1/Th2 ratio correlated with most of the following indexes: TNF-α, IL-1β, IL-6, C-reactive protein, sequential organ failure assessment (SOFA) score, or Acute Physiology and Chronic Health Evaluation II (APACHE II) score (most p < 0.05). Moreover, miR-451a (p < 0.001) and the Th1/Th2 ratio (p = 0.001) increased in deaths compared to survivors of sepsis; further ROC curve showed both miR-451a and the Th1/Th2 ratio possessed a certain value to predict mortality of patients with sepsis. Additionally, the Th1/Th2 ratio [odds ratio (OR): 2.052, p = 0.005] was independently related to 28-day mortality risk from multivariate logistic regression.ConclusionMiR-451a correlates with the Th1/Th2 ratio, and they both relate to inflammation, septic organ injury, and mortality risk in patients with sepsis.

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Overexpression of miR-451a in sepsis and septic shock patients is involved in the regulation of sepsis-associated cardiac dysfunction and inflammation

Cited by 11 publications

References 40 publications

Clinical Significance of the Serum lncRNA NORAD Expression in Patients with Neonatal Sepsis and Its Association with miR-410-3p

Clinical Significance of the Serum lncRNA NORAD Expression in Patients with Neonatal Sepsis and Its Association with miR-410-3p

MicroRNA-381-3p signatures as a diagnostic marker in patients with sepsis and modulates sepsis-steered cardiac damage and inflammation by binding HMGB1

MicroRNA-451a and Th1/Th2 ratio inform inflammation, septic organ injury, and mortality risk in sepsis patients

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