Abstract
Sepsis is a common cause of death among patients in intensive care unit. Recent evidence indicates that microRNAs (miRs) might serve as potential biomarkers facilitating an early diagnosis of sepsis. Herein, we aimed to examine the mechanisms by which miR-590-3p may regulate inflammatory response and organ dysfunction during sepsis progression. The Gene Expression Omnibus (GEO) database was used to identify differentially expressed genes in an established sepsis mouse model, and the related miRNAs and downstream regulatory pathways were predicted using web-available microarrays. A sepsis animal model was induced in mice by cecal ligation and puncture (CLP). Indices of cardiac function, serum myocardial enzymes, and organ function were measured to confirm successful generation of the sepsis mouse model. Cell apoptosis and inflammatory cytokine levels in lung and liver tissues were observed by TUNEL staining and ELISA. Furthermore, the interaction between miR-590-3p and Synapse-associated protein 1 (Syap1) was identified by dual luciferase reporter gene assay. The effect of miR-590-3p on inflammation and organ dysfunction was examined using gain- and loss-of-function experiments. Syap1 was found poorly expressed, whereas miR-590-3p was highly expressed in the sepsis-affected mice. Moreover, the elevation of miR-590-3p markedly downregulated the expression of anti-inflammatory cytokines IL10, Syap1, TGF-β, Smad3, and NF-кB p65 in modeled mice. Indices of cardiac and organ function were decreased, serum myocardial enzyme indices were notably increased, and cell apoptosis and pro-inflammatory cytokines of lung and liver tissues were increased in modeled mice. Together these results demonstrated that miR-590-3p can block the TGF-β/Smad signaling pathway through downregulation of Syap1 and, thereby, contribute to sepsis inflammation and organ dysfunction.
Sirtuin 3 Activation by Honokiol Decreases Unilateral Ureteral Obstruction-Induced Renal Inflammation and Fibrosis via Regulation of Mitochondrial Dynamics and the Renal NF-κB-TGF-β1/Smad Signaling Pathway
