MiR-21 expression was decreased in sepsis patients compared with HCs, and further receiver operating characteristic (ROC) curve analysis revealed that miR-21 was of a good value in predicting sepsis risk (area under the curve [AUC]: 0.801, 95% CI: 0.758-0.844).
<b>Conclusion:</b> This study demonstrates a critical role for exosomal miR-21 in renoprotection conferred by limb rIPC against sepsis and suggests that rIPC and exosomes might serve as the possible therapeutic strategies for sepsis-induced kidney injury.
The T allele of the miR-21 SNP rs13137 and the T allele of the miR-145 SNP rs353291 (OR = 0.685, 95% CI = 0.566-0.820, P < .001) were found to be a protective factor for sepsis (OR = 0.755, 95% CI = 0.632-0.896, P < .001).
These results demonstrate that S100A9 promotes MDSC expansion and immunosuppression in late/chronic sepsis by inducing the expression of miR-21 and miR-181b.
Our results support a myeloid cell loop in which NFI-A and miR-21 and miR-181b sustain Gr1<sup>+</sup>CD11b<sup>+</sup> MDSC-dependent immunosuppression during sepsis.
MicroRNA-21 is required for local and remote ischemic preconditioning in multiple organ protection against sepsis, and up-regulation of miR-21 may be a potential therapy for sepsis.
Surprisingly, we find that intracellular S100A9 protein translocates from the cytosol to nucleus in Gr1<sup>+</sup>CD11b<sup>+</sup> MDSCs during late sepsis and promotes expression of miR-21 and miR-181b immune repressor mediators.
Mechanistically, transcription factor Rb phosphorylation supports Stat3 and C/EBPβ accumulation at both miRNA promoters, and C/EBPβ or Stat3 depletion by siRNA in sepsis Gr1<sup>+</sup>CD11b<sup>+</sup> MDSCs inhibits miR-21 and miR-181b expression.
The results were shown that miRNA-21 over-expression had effects to protect kidney cell apoptosis induced by sepsis via PTEN/PI3K/AKT signaling pathway.
Thus, by stimulating proinflammatory PDCD4 and decreasing the abundance of miR-21, decorin signaling boosts inflammatory activity in sepsis and suppresses tumor growth.