MiR-124-3p helps to protect against acute respiratory distress syndrome by targeting p65

Abstract

Background: Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury that has a high mortality rate and leads to substantial healthcare costs. MicroRNA-124-3p (miR-124-3p) helps to suppress inflammation during a pulmonary injury. However, its mechanism of action is largely unknown, and its role in ARDS remains to be determined. Methods: Mice and NR8383 cells were exposed to lipopolysaccharides (LPS) to induce ARDS, and their miR-124-3p levels were determined. After a miRNA agomir was administrated to the mice, their pulmonary injuries were evaluated by H&E staining and assays for peripheral inflammatory cytokine levels. The direct interaction between miR-124-3p and p65 was predicted, and then confirmed by a luciferase activity assay. The role played by miRNA-124-3p in regulating p65 expression was further examined by transfection with its agomir, and its role in cell apoptosis was investigated by observing the effects of miRNA overexpression in vitro and in vivo. Results: After exposure to LPS, there was a consistent decrease in miR-124-3p expression in the lungs of mice and in NR8383 cells. After treatment with the miR-124-3p agomir, the degrees of pulmonary injury (e.g. alveolar hemorrhage and interstitial edema), and the increases in IL-1β, IL-6, and TNF-α levels induced by LPS were significantly attenuated. Overexpression of miR-124-3p in NC8383 cells and lung tissues significantly suppressed LPS-induced p65 expression and cell apoptosis. Conclusions: These results suggest that miR-124-3p directly targeted p65, and thereby decreased the levels of inflammation and pulmonary injury in a mouse model of ARDS.

MicroRNAs based regulation of cytokine regulating immune expressed genes and their transcription factors in COVID-19

“…A mice model showed downregulation in miR-124-3p expression in ARDS. Treatment with miR-124-3p agomir attenuated the pulmonary injury and the levels of pro-inflammatory cytokines IL-6 and TNF-α by directly targeting p65, thus showing promise in in-vitro management of pulmonary injury ( Liang et al, 2020 , p. 65).…”

Roles of Macrophage Polarization and Macrophage-Derived miRNAs in Pulmonary Fibrosis

“…There have also been reports of miR-124 acting to attenuate M1 macrophages as a universal regulator of macrophage into the M2 subtype by decreasing NFκB activity in various subsets of monocytic cells and tissue-resident macrophages including lung macrophages ( 65 , 66 ). The dysregulation of miR-142-5p and miR-130a-3p was characterised as an important factor governing the polarization of macrophages with higher levels of M2-like phenotypic markers and was associated with airway remodelling in ovalbumin-sensitized mice ( 67 ).…”

Insights into the SARS-CoV-2-Mediated Alteration in the Stress Granule Protein Regulatory Networks in Humans

“…Moreover, hsa-miR-124-3p was found to be downregulated in JEV-infected human neural stem cells [61]. The miR-124-3p agomir reduced pro-inflammatory cytokines IL-6 and TNF-α levels and thus was able to protect against pulmonary injury [62]. It has been shown that SARS-CoV-2 hijacks Ddx58 which is involved in miRNA biogenesis and mRNA splicing to help its replication.…”