microRNA-23b regulates the expression of inflammatory factors in vascular endothelial cells during sepsis

Abstract

miR-23b is a multifunctional microRNA that contributes to the regulation of multiple signaling pathways. It has been reported that miR-23b prevents multiple autoimmune diseases through the regulation of inflammatory cytokine pathways. In addition, the function and underlying mechanisms of miR-23b on sepsis are currently being investigated. In the present study, miR-23b inhibitor and mimics sequences were transfected into human vascular endothelial cells to inhibit and upregulate the expression of miR-23b, respectively. In addition, respective negative control (NC) sequences were transfected. The expression of miR-23b was found to be downregulated in the cells transfected with the mimics NC or inhibitor NC sequences following stimulation with lipopolysaccharide (LPS; P<0.01); however, higher expression levels were maintained in the cells transfected with the mimics sequence and very low levels were observed in the cells transfected with the inhibitor sequence. In addition, the expression levels of nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α, interleukin (IL)-6, intercellular adhesion molecule (ICAM)-1, E-selectin and vascular cell adhesion molecule (VCAM)-1 were shown to increase following induction by LPS in the cells transfected with inhibitor/mimics NC sequences (P<0.05). However, the expression levels of these inflammatory factors decreased in the cells transfected with the mimics sequence, and increased to a greater degree in the cells transfected with the inhibitor sequence, as compared with the inhibitor NC sequences (P<0.05). Therefore, miR-23b may play a significant role in the pathogenesis and progression of sepsis by inhibiting the expression of inflammatory factors, including NF-κB, TNF-α, IL-6, ICAM-1, E-selectin and VCAM-1.

Non-Lethal Endotoxin Injection: A Rat Model of Hypercoagulability

“…Among the individual miRNAs previously associated with endothelial cell and monocyte activation and sepsis in humans and rodents [27–29], we found increases in our study of miR-16, miR-21, miR-126, miR-146a, miR-150, miR-511, and miR-23b. The adhesion and hemostatic proteins monitored in our study, sICAM-1, E-selectin, fibrinogen, and PAI-1 have been identified as targets of miRNA regulation in human cell cultures and clinical patients [29–33]. Of the 46 increased miRNA, sICAM-1 was the predicted target of 6 (miR-23b, miR-27a, miR-99a, miR-100, miR-324-5p, miR-363); PAI-1 was the predicted target of 4 (miR-30a, miR-30d, miR-182, miR-384-5p), E selectin the predicted target of 2 (miR-16; miR-195) and the alpha chain of fibrinogen the predicted target of miR-29c [26].…”

“…Many of these miRNAs have been associated with the signaling pathways in humans for toll-like receptor 4 (TLR4), TGF-beta, and pro-inflammatory cytokines, the complement and coagulation cascades, and processes such as leukocyte migration [26]. Among the individual miRNAs previously associated with endothelial cell and monocyte activation and sepsis in humans and rodents [27–29], we found increases in our study of miR-16, miR-21, miR-126, miR-146a, miR-150, miR-511, and miR-23b. The adhesion and hemostatic proteins monitored in our study, sICAM-1, E-selectin, fibrinogen, and PAI-1 have been identified as targets of miRNA regulation in human cell cultures and clinical patients [29–33].…”

miR-23b targets Smad 3 and ameliorates the LPS-inhibited osteogenic differentiation in preosteoblast MC3T3-E1 cells

“…The LPS-downregulated miR-210 also negatively regulated the LPS-induced production of proinflammatory cytokines by targeting NF-κB1 (Qi et al, 2012). miR-23b is a newly identified oncogenic miRNA, which is upregulated in sepsis in response to the stimulation of LPS (Wu et al, 2015). In the current study, we found that the miR-23b induction was markedly downregulated by the stimulation of LPS in the preosteoblast MC3T3-E1 cells.…”

“…In addition, the inhibitory role of miR-23b has been confirmed in autoimmune diseases (Hu and O'Connell, 2012). Moreover, miR-23b has been demonstrated to be downregulated in sepsis in response to the stimulation of LPS (Wu et al, 2015). However, the regulation of miR-23b in osteoblasts has not been investigated.…”

The Expression of Nuclear Transcription Factor Kappa B (NF-κB) in the Case of Critically Ill Polytrauma Patients with Sepsis and Its Interactions with microRNAs

“…A similar study performed by Olarein-George et al, in which he studied the role of microRNA-517a and microRNA-517c in NFjB activity, reports of which stated that there exists a significant correlation from the modelling point of view (Olarerin-George et al 2013). Another study performed by Wu et al, proved that increase in microRNA-23b expression alters the functioning of NF-jB and thus augments the sepsis (Wu et al 2015). According to the study by Sun et al, it was evident that microRNA-181b modulates not only the NF-jB activity but also the inflammatory response (Sun et al 2012).…”