MicroRNA-574-5p Attenuates Acute Respiratory Distress Syndrome by Targeting HMGB1

Abstract

Acute respiratory distress syndrome (ARDS) is a critical condition with high mortality. HMGB1 (high-mobility group protein B1) is one of the key proinflammatory factors in the ARDS “inflammatory storm.” According to previous studies, some microRNAs (miRNAs) play important roles in this process. We aimed to determine the contributing miRNAs targeting the expression and release of HMGB1. miRNA expression in the peripheral blood of patients with ARDS was measured by miRNA microarray. miRNAs targeting HMGB1 were screened and explored for further study. In LPS-induced cell and mouse ARDS models, we explored the effect of this miRNA on the expression and secretion of HMGB1 by Western blot, real-time qPCR, and ELISA. The effects of this miRNA on the NF-κB signaling pathway, proinflammatory cytokines, and NLRP3 (nod-like receptor protein 3) inflammasome were detected by Western blot and real-time qPCR. In ARDS models, microRNA-574-5p (miR-574-5p) expression could be induced by the TLR4/NF-κB pathway upon LPS stimulation. It could suppress the inflammatory response by targeting HMGB1. Enforcing the expression of miR-574-5p or HMGB1 siRNA silencing inhibits the activation of NF-κB signaling pathway and the NLRP3 inflammasome. Moreover, overexpression of HMGB1 reversed the antiinflammatory effect of miR-574-5p. In ARDS mice, overexpression of miR-574-5p suppresses alveolar leukocytes infiltration, interstitial edema, protein effusion, and inflammation. This study demonstrated that miR-574-5p provided negative feedback to LPS-induced inflammation and relieved ARDS. It may provide new therapeutic strategies for ARDS.

Circulating miRNAs as Promising Biomarkers to Evaluate ECMO Treatment Responses in ARDS Patients

“…Furthermore, as shown in Figure 6 , those miRNAs can help classify ARDS patients in relation to the timing of their ECMO course, and we were able to reach a discriminatory power with AUC ranged from 0.52 to 0.92 ( Figure 7 ). Our results are also in line with several studies that show that some of our deregulated miRNAs were implicated in ARDS pathogenesis [ 16 , 30 , 57 ]. In addition, the present data sustain, at the miRNA level (at a deeper cell and system interaction), the clinical evidence that during ARDS and during ECMO, a consistent activation of pro-coagulant and anticoagulant pathways coexist at the same time.…”

Loss of MBD2 ameliorates LPS‐induced alveolar epithelial cell apoptosis and ALI in mice via modulating intracellular zinc homeostasis

“…29,58 Second, LPS extracted from a single strain of bacteria (E. coli 055:B5) was used in accordance with previous reports. 40,59 The use of an alternate animal model or source of LPS would enhance the generalization of the conclusion we have presented in this study. Moreover, in vivo modulation of MBD2 other than genomic knockout was beyond the scope of our current study.…”

Dexmedetomidine hydrochloride inhibits hepatocyte apoptosis and inflammation by activating the lncRNA TUG1/miR-194/SIRT1 signaling pathway

“…Thus, our data were in line with the function of SIRT1, confirming that TUG1 mediated the inflammatory responses via indirectly targeting SIRT1. On the other hand, NLRP3 is known to be an inflammasome, and it can promote the levels of inflammatory cytokines in organ respiration [49,50]. It was found that SIRT1 inhibited the activation of NLRP3 and the secretion of IL-1β in cerebral ischemia [51].…”