MicroRNA‑21 inhibits lipopolysaccharide‑induced acute lung injury by targeting nuclear factor‑κB

Abstract

Acute lung injury (ALI) is a frequent, but severe complication following sepsis in patients with critical illness. The present study aimed to investigate the potential role of microRNA-21 (miR-21) in the regulation of inflammation in the ALI induced by lipopolysaccharide (LPS) in vitro and in vivo. The levels of inflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β and IL-10, and the level of miR-21 expression were measured in the lungs of LPS-induced ALI rats and NR8383 alveolar macrophages (AMs). To confirm the regulatory effect of miR-21 in the inflammatory reactions of ALI, NR8383 cells were transfected with a mimic of miR-21 or an anti-miR-21 inhibitor, and the subsequent changes of the miR-21 level and the levels of inflammatory cytokines were detected. The underlying molecular mechanism was also investigated. LPS-induced ALI in rats resulted in significant overexpression of pro-inflammatory cytokines, TNF-α, IL-6 and IL-1β, and miR-21, but reduced the expression of the anti-inflammatory cytokine IL-10. LPS treatment also led to a higher expression level of miR-21 and increased secretion of pro-inflammatory cytokines in NR8383 cells in a time-dependent manner. Manipulation with the miR-21 mimic significantly suppressed the LPS-mediated induction of TNF-α, IL-6 and IL-1β in NR8383 cells, while that induction was upregulated when miR-21 expression was silenced via transfection with the anti-miR-21 inhibitor. Further mechanism experiments revealed that miR-21 regulates LPS-induced inflammation responses via the Toll-like receptor 4 and nuclear factor-κB (Nf-κB) signaling pathway. miR-21 negatively regulates inflammatory responses in LPS-induced ALI by targeting the NF-κB signaling pathway, providing further insight into the molecular mechanism of ALI progression.

Lnc‐MEG3 acts as a potential biomarker for predicting increased disease risk, systemic inflammation, disease severity, and poor prognosis of sepsis via interacting with miR‐21

“…7,8 As for miR-21, it has been proposed as a regulator that elicits effect on inhibiting inflammatory responses and protecting several vital organs from damage in sepsis. 10,11 Based on the effects of lnc-MEG3 and miR-21 on inflammation and organ injury as well as the interaction between lnc-MEG3 and miR-21, we speculated that and alleviated tissue damage as well as organ dysfunctions, thereby, leading to lower levels of inflammation and attenuated disease severity in sepsis patients. 11 Notably, lnc-MEG3/miR-21 axis exhibited relatively higher correlation coefficients with disease severity (APACHE II score and SOFA score) compared with lnc-MEG3 and miR-21 individually, which implied that lnc-MEG3/miR-21 axis was with better clinical value in sepsis progression.…”

“…5,7,8 Among these target miRNAs, miR-21 functions as an important contributor for preventing inflammation and organ dysfunctions such as liver, kidney, and lung in sepsis. [9][10][11] Based on these previous studies, we hypothesized that lnc-MEG3 might be involved in the development and progression of sepsis via interacting with miR-21. Therefore, this study aimed to investigate the correlations of lnc-MEG3, miR-21 and lnc-MEG3/miR-21 axis with disease risk, inflammation, disease severity, and 28-day mortality of sepsis.…”

The predictive value of microRNA‐21 for sepsis risk and its correlation with disease severity, systemic inflammation, and 28‐day mortality in sepsis patients

“…MicroRNAs (MiRNAs) are a class of small non‐coding endogenous molecules RNA (approximately 19‐25 nucleotides in size), which regulate gene expression at post‐transcriptional level by influencing the stability and translation of mRNA . MicroRNA (miR)‐21, a commonly studied miRNA, is shown to regulate inflammation and several organ injuries in the pathogenesis of sepsis . For instance, miR‐21 suppresses lipopolysaccharide (LPS)‐induced inflammation through the toll‐like receptor 4 and nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) pathway in sepsis .…”

“…6 MicroRNA (miR)-21, a commonly studied miRNA, is shown to regulate inflammation and several organ injuries in the pathogenesis of sepsis. [7][8][9] For instance, miR-21 suppresses lipopolysaccharide (LPS)-induced inflammation through the toll-like receptor 4 and nuclear factor kappa-light-chainenhancer of activated B cells (NF-κB) pathway in sepsis. 8 Another study illuminates that upregulation of miR-21 decreases apoptosis and proinflammatory cytokines production in kidneys, hearts, livers, and lungs, implying that miR-21 exerts protective effect on multiple organ failure induced by sepsis.…”

“…[7][8][9] For instance, miR-21 suppresses lipopolysaccharide (LPS)-induced inflammation through the toll-like receptor 4 and nuclear factor kappa-light-chainenhancer of activated B cells (NF-κB) pathway in sepsis. 8 Another study illuminates that upregulation of miR-21 decreases apoptosis and proinflammatory cytokines production in kidneys, hearts, livers, and lungs, implying that miR-21 exerts protective effect on multiple organ failure induced by sepsis. 9 Given the effect of miR-21 on inflammation inhibition and organ protection in sepsis, we hypothesized that miR-21 might serve as a potential biomarker for assessing sepsis risk and prognosis of sepsis.…”