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Sepsis-associated acute kidney injury (S-AKI) is a common disease in pediatric intensive care units (ICU) with high morbidity and mortality. The newly discovered results indicate that microRNAs (miRNAs) play an important role in the diagnosis and treatment of S-AKI and can be used as markers for early diagnosis. In this study, the expression level of miR-16-5p was found to be significantly upregulated about 20-fold in S-AKI patients, and it also increased by 1.9 times in the renal tissue of S-AKI mice. Receiver operating characteristic (ROC) curve analysis showed that miR-16-5p had the highest predictive accuracy in the diagnosis of S-AKI (AUC = 0.9188). In vitro, the expression level of miR-16-5p in HK-2 cells treated with 10 μg/mL lipopolysaccharide (LPS) increased by more than 2 times. In addition, LPS-exposed renal tissue and HK-2 cells lead to upregulation of inflammatory cytokines IL-6, IL-1β, TNF-a, and kidney damage molecules kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL). However, inhibition of miR-16-5p significantly mitigated LPS expose-mediated kidney injury and inflammation. Furthermore, LPS-exposed HK-2 cells increased more than 1.7-fold the expression levels of Bax and caspase-3, decreased 3.2-fold the expression level of B-cell lymphoma-2 (Bcl-2), and significantly promoted the occurrence of apoptosis. MiR-16-5p mimic further increased LPS-induced apoptosis in HK-2 cells. Nevertheless, inhibition of miR-16-5p significantly attenuated this effect. In summary, up-regulation of miR-16-5p expression can significantly aggravate renal injury and apoptosis in S-AKI, which also proves that miR-16-5p can be used as a potential biomarker to promote early identification of S-AKI. [ABSTRACT FROM AUTHOR]

Activation of endothelial cells plays a key role in septic acute kidney injury (AKI). This study investigated the role of miRNA in endothelial-induced tubular cell injury in sepsis. Circulating endothelial cells (CECs) from septic AKI, non-septic AKI, septic non-AKI patients and healthy volunteers were isolated and cultured, and HK2 cells were exposed to CEC-conditioned medium. CEC-conditioned medium prepared from septic AKI patients led to cell shrinkage, decreased E-cadherin, the release of NAG and cell apoptosis in HK2 cells. TNF-α mediated the tubular cell injury induced by CEC-conditioned medium prepared from septic AKI patients. PCR array analysis detected that miR-107 was significantly increased in the CECs of septic AKI patients. MiR-107 was verified to target the 3′UTR of Dual-specificity phosphatase 7(DUSP7). Transfection of miR-107 ASO recovered the expression of DUSP7, suppressed the phosphorylation of ERK, and decreased the secretion of TNF-α in the CECs of septic AKI patients and in the peritubular endothelial cells of septic AKI mice. The inhibition of miR-107 prevented the decrease of E-cadherin, the release of NAG and cell apoptosis in HK2 cells exposed to CEC-conditioned medium prepared from septic AKI patients, and preserved the normal renal morphology and decreased the serum creatinine level in septic AKI mice. In conclusion, our study suggests that the increased miR-107 induces TNF-α secretion by targeting DUSP7 in endothelial cells, which may directly cause tubular cell injury in septic AKI. [ABSTRACT FROM AUTHOR]