miR-23b Negatively Regulates Sepsis-Induced Inflammatory Responses by Targeting ADAM10 in Human THP-1 Monocytes

Zhang, Wenying; Lu, Fanghong; Xie, Yan; Lin, Yao; Zhao, Tian; Tao, Shoubao; Lai, Zhipeng; Wei, Ning; Yang, Ruoxuan; Shao, Yiming; He, Junbing

doi:10.1155/2019/5306541

Cited by 24 publications

(22 citation statements)

References 42 publications

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“…Currently, some aberrantly expressed miRNAs have been identified in sepsis. For example, the decreased miR-23b expression detected in the peripheral blood mononuclear cells of sepsis patients was negatively correlated with inflammatory response and could alleviate the LPS-stimulated inflammatory cytokines [24]. The decreased expression of miR-21 was reported in patients with sepsis and exhibited a good value to predict sepsis risk and thus was determined as a candidate biomarker for the development and progression of sepsis [25].…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Value of miR-103 in Patients with Sepsis and Noninfectious SIRS and Its Regulatory Role in LPS-Induced Inflammatory Response by Targeting TLR4

Yang

Zhao

Sun

2020

International Journal of Genomics

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Background. Sepsis is a life-threatening condition and a systemic inflammatory response syndrome (SIRS) driven by infection. This study aimed at investigating the expression of microRNA-103 (miR-103) in sepsis patients, evaluating its diagnostic value, and exploring the regulatory effect of miR-103 on LPS-induced inflammation in monocytes. Methods. Expression of miR-103 was measured using quantitative real-time PCR. A receiver operating characteristics curve was plotted to evaluate the diagnostic vale of miR-103. Serum and cell supernatant levels of proinflammatory cytokines were analyzed using ELISA. The interaction between miR-103 and Toll-like receptors 4 (TLR4) was analyzed using luciferase reporter assay. The effect of miR-103 on inflammation was examined in LPS-treated monocytes. Results. Serum expression of miR-103 was decreased in noninfectious SIRS and sepsis patients compared with healthy controls, and the lowest expression value was observed in sepsis patients (all P<0.05). Serum levels of miR-103 have considerable diagnostic accuracy in distinguishing sepsis patients from SIRS patients and healthy controls. A negative correlation was found between miR-103 and inflammatory responses in sepsis patients. TLR4 was demonstrated to be a direct target of miR-103 and was negatively regulated by miR-103 in monocytes. The promoted inflammatory responses by LPS in monocytes were reversed by the overexpression of miR-103. Conclusion. All the data revealed that serum decreased miR-103 in sepsis patients serves as a promising noninvasive diagnostic biomarker and may be involved in the pathogenesis of sepsis by regulating inflammatory responses via targeting TLR4.

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Section: Discussionmentioning

confidence: 99%

Diagnostic Value of miR-103 in Patients with Sepsis and Noninfectious SIRS and Its Regulatory Role in LPS-Induced Inflammatory Response by Targeting TLR4

Yang

Zhao

Sun

2020

International Journal of Genomics

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“…lPS is an endotoxin that is able to regulate the development of myocardial injury caused by sepsis (22), and has been widely used to induce sepsis models in vitro (23,24). in the present study, 1 µg/ml LPS was used to treat HMEC-1 cells.…”

Section: Discussionmentioning

confidence: 99%

Potential role of lncRNA HULC/miR‑128‑3p/RAC1 axis in the inflammatory response during LPS‑induced sepsis in HMEC‑1 cells

et al. 2020

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Sepsis is a serious clinical condition characterized by systemic inflammation. The long noncoding rna (lncrna) highly upregulated in liver cancer (Hulc) was validated to partake in the development of sepsis. The present study aimed to investigate the potential mechanism of Hulc in lipopolysaccharide (lPS)-induced sepsis. reverse transcription-quantitative polymerase chain reaction (rT-qPcr) and western blot analysis was employed to examine the expression of Hulc, microrna (mir)-128-3p, rac family small GTPase 1 (RAC1) and pro-inflammatory factors [IL-6, TnF-α, intercellular adhesion molecule (icaM1) and vascular cell adhesion molecule (VcaM1)] in the serum of patients with sepsis or lPS-induced human dermal microvascular endothelial cells (HMec-1). Flow cytometry and western blot assays were performed to detect cell apoptosis. The targeted relationship among HULC, miR-128-3p and RAC1 was confirmed by a dual-luciferase reporter assay, rna binding protein immunoprecipitation (riP) assay and rna pull-down assay. Hulc and rac1 were found to be upregulated, and mir-128-3p was downregulated in the serum of patients with sepsis and lPS-stimulated HMec-1 cells. lPS promoted apoptosis and inflammation, which were decreased by silencing of HULC. Hulc targeted mir-128-3p and negatively regulated its expression. Hulc knockdown protected HMec-1 cells from lPS-induced injury by upregulating mir-128-3p. rac1 was a target of mir-128-3p, and gain of rac1 also relieved the silencing of Hulc-mediated suppressive effects on apoptosis and inflammation in LPS-stimulated HMEC-1 cells. In conclusion, Hulc knockdown partially reversed lPS-induced sepsis via the regulation of mir-128-3p/rac1 axis.

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“…In sepsis, miR-23b has been reported to be down-regulated in peripheral blood mononuclear cells (PBMCs) from adult patients and in the LPS-induced THP-1 human monocytic cell line, and has been negatively correlated with the production of proin ammatory cytokines. Increased miR-23b expression has been shown to induce the down-regulation of proin ammatory cytokines production and LPSstimulated apoptosis [19].…”

Section: Change In the Mirna-23b Expression Levels In Newborns In Twomentioning

confidence: 99%

“…This discovery opens up new therapeutic pathways in late stages of the septic phase [18]. Finally, another study demonstrates that miR-23b is an anti-in ammatory factor that negatively regulates the in ammatory responses induced by lipopolysaccharide (LPS) by targeting metalloproteinase 10 (ADAM10) [19].…”

Section: Introductionmentioning

confidence: 97%

miRNA-23b as a biomarker of culture-positive neonatal sepsis

Fatmi¹,

Rebiahi

Chabni

et al. 2020

Preprint

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Background: Neonatal sepsis remains an important cause of morbidity and mortality. The ability to quickly and accurately diagnose neonatal sepsis based on clinical assessments and laboratory blood tests remains difficult, where haemoculture is the gold standard for detecting bacterial sepsis in blood culture. It is also very difficult to study because neonatal samples are lacking. Methods : Forty-eight newborns suspected of sepsis admitted to the Neonatology Department of the Mother-Child Specialized Hospital of Tlemcen. From each newborn, a minimum of 1-2 ml of blood was drawn by standard sterile procedures for blood culture. The miRNA-23b level in haemoculture was evaluated by RT-qPCR. Results : miR-23b levels increased in premature and full-term newborns in early onset sepsis ( p < 0.001 and p < 0.005 respectively), but lowered in late onset sepsis in full-term neonates ( p < 0.05) compared to the respective negative controls. miR-23b levels also increased in late sepsis in the negative versus early sepsis negative controls ( p < 0.05). miR-23b levels significantly lowered in the newborns who died from both sepsis types ( p < 0.0001 and p < 0.05 respectively). In early sepsis, miR-23b and death strongly and negatively correlated (correlation coefficient = -0.96, p = 0.0019). In late sepsis, miRNA-23b and number of survivors (correlation coefficient = 0.70, p = 0.506) positively correlated. Conclusions : Lowering miR-23b levels is an important factor that favours sepsis development, which would confirm their vital protective role, and strongly suggest that they act as a good marker in molecular diagnosis and patient monitoring.

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miR-23b Negatively Regulates Sepsis-Induced Inflammatory Responses by Targeting ADAM10 in Human THP-1 Monocytes

Cited by 24 publications

References 42 publications

Diagnostic Value of miR-103 in Patients with Sepsis and Noninfectious SIRS and Its Regulatory Role in LPS-Induced Inflammatory Response by Targeting TLR4

Diagnostic Value of miR-103 in Patients with Sepsis and Noninfectious SIRS and Its Regulatory Role in LPS-Induced Inflammatory Response by Targeting TLR4

Potential role of lncRNA HULC/miR‑128‑3p/RAC1 axis in the inflammatory response during LPS‑induced sepsis in HMEC‑1 cells

miRNA-23b as a biomarker of culture-positive neonatal sepsis

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