miR-128-3p enhances the protective effect of dexmedetomidine on acute lung injury in septic mice by targeted inhibition of MAPK14

Abstract

Background: To investigate the role of miR-128-3p and MAPK14 in the dexmedetomidine treatment of acute lung injury in septic mice. Methods: SPF C57BL/6 mice were divided into 8 groups. The pathological changes and wet/dry weight ratio (W/D), PaO 2 , PaCO 2 , MDA, SOD and MPO levels in lung tissue and the serum levels of inflammation factors were observed. Dual luciferase reporter assay was used to detect the targeting relationship of miR-128-3p and MAPK14, and qPCR and WB were used to detect the expression of miR-128-3p and MAPK14. Results: Compared with the Normal group, other groups had lower MDA, MPO, inflammatory factors levels and the expression level of MAPK14, while the content of SOD and the expression level of miR-128-3p was significantly decreased (all p < 0.05). Compared with the Model group, the contents of MDA, MPO, inflammatory factors in the DEX group and miR-128-3p mimic group were significantly decreased, and the content SOD was significantly increased, however, opposite results were occurred in oe-MAPK14 group (all p < 0.05). Compared with the DEX group, all the indicators in miR-128-3p mimic+DEX group showed significant improvement (all p < 0.05). Compared with the miR-128-3p mimic group, all the indicators were deteriorated in the miR-128-3p mimic+oe-MAPK14 group (all p < 0.05). The combination of DEX and oe-MAPK14 blocked the protective effect of dexmedetomidine on acute lung injury in septic mice. Conclusion: miR-128-3p can further enhance the protective effect of dexmedetomidine on acute lung injury in septic mice by targeting and inhibiting MAPK14 expression.

Down-regulation of SNHG16 alleviates the acute lung injury in sepsis rats through miR-128-3p/HMGB3 axis

“…Ding et al took the lead in research and proved that miR-128-3p promotes the SOD expression while down-regulates MPO and MDA in septic mouse tissues. Meanwhile, miR-128-3p enhances the protection of dexmedetomidine against ALI in sepsis mice by targeting and dampening MAPK14 [ 15 ]. Above all, some studies have found that down-regulated SNHG16 inhibits HOXA7 by sponging miR-128-3p to prevent the development of glioblastoma [ 30 ].…”

“…Studies by Pan et al illustrated that miR-128-3p is knocked down in lung cancer tissues and cell lines, which is helpful for the diagnosis of early lung cancer [ 14 ]. Moreover, miR-128-3p facilitates the protection of dexmedetomidine against ALI in sepsis mice by dampening MAPK14 [ 15 ]. Hence, miR-128-3p has the potential effect in preventing lung injury.…”

Identification of the TF-miRNA-mRNA co-regulatory networks involved in sepsis

“…Therefore, with the progression of sepsis and septic shock, MAPK14 would be upregulated. Li et al reported that miR-128-3p could enhance the protective effect of dexmedetomidine on acute lung injury (ALI) in a septic mouse model by inhibiting MAPK14 expression [27] . Pan et al have also found that miR-124 could alleviate acute lung injury symptoms of by inhibiting the activation of the MAPK signaling pathway via inhibiting MAPK14 expression [28] .…”

Atractylenolide III alleviates sepsis-mediated lung injury via inhibition of FoxO1 and VNN1 protein

“…Lung damage, a prevalent complication of sepsis, gives rise in multiple organ dysfunction syndrome, as well as death of those who suffer from it 22 . The perfect target for treating sepsis-mediated lung damage is to inhibit inflammatory response, prevent apoptosis, and maintain lung function [23][24][25] . Nevertheless, the causative role of sepsis-mediated lung damage is still distinct, which immensely impedes the screening of diagnostic markers of sepsis-mediated lung injury.…”