Exosomes from patients with septic shock convey miRNAs related to inflammation and cell cycle regulation: new signaling pathways in sepsis?

BACKGROUND: Exosomes isolated from plasma of patients with sepsis may induce vascular apoptosis and myocardial dysfunction by mechanisms related to inflammation and oxidative stress. Despite previous studies demonstrating that these vesicles contain genetic material related to cellular communication, their molecular cargo during sepsis is relatively unknown. In this study, we evaluated the presence of microRNAs (miRNAs) and messenger RNAs (mRNAs) related to inflammatory response and redox metabolism in exosomes of patients with septic shock. METHODS: Blood samples were collected from 24 patients with septic shock at ICU admission and after 7 days of treatment. Twelve healthy volunteers were used as control subjects. Exosomes were isolated by ultracentrifugation, and their miRNA and mRNA content was evaluated by qRT-PCR array. RESULTS: As compared with healthy volunteers, exosomes from patients with sepsis had significant changes in 65 exosomal miRNAs. Twenty-eight miRNAs were differentially expressed, both at enrollment and after 7 days, with similar kinetics (18 miRNAs upregulated and 10 downregulated). At enrollment, 35 differentially expressed miRNAs clustered patients with sepsis according to survival. The pathways enriched by the miRNAs of patients with sepsis compared with control subjects were related mostly to inflammatory response. The comparison of miRNAs from patients with sepsis according to hospital survival demonstrated pathways related mostly to cell cycle regulation. At enrollment, sepsis was associated with significant increases in the expression of mRNAs related to redox metabolism (myeloperoxidase, 64-fold; PRDX3, 2.6-fold; SOD2, 2.2-fold) and redox-responsive genes (FOXM1, 21-fold; SELS, 16-fold; GLRX2, 3.4-fold). The expression of myeloperoxidase mRNA remained elevated after 7 days (65-fold). CONCLUSIONS: Exosomes from patients with septic shock convey miRNAs and mRNAs related to pathogenic pathways, including inflammatory response, oxidative stress, and cell cycle regulation. Exosomes may represent a novel mechanism for intercellular communication during sepsis.

Expression of aquaporin 2 following facial nerve crush in rats.

CONCLUSION: We demonstrated an early increase in aquaporin 2 (AQP2) expression in a motor nerve (extratemporal facial nerve, FN) following acute peripheral compression (crush), concomitant to effective development of motor dysfunction (facial palsy). The early increase in AQP2 expression that occurred concomitantly with the appearance of a deficit in a peripheral motor nerve suggests that this protein is involved in the physiological events associated with post-injury edema, similar to the already demonstrated behavior of AQP4 in the central nervous system (CNS). OBJECTIVE: The aim of this study was to assess the expression of AQP2 in the FN of rats up to 7 days after crush. METHODS: The extratemporal trunk of the right FN of rats was subjected to mechanical crush, and the expression of AQP2 in the affected (right) and non-affected (left) FN was measured by means of western blotting at days 1, 3, and 7 after injury. Behavioral analysis of the development of facial palsy was also performed over the same time period. RESULTS: Increased expression of AQP2 was shown in the affected FN compared with its corresponding control at day 1 after compression, simultaneously with the appearance of facial palsy.