miRNA-770-5p expression is upregulated in patients with type 2 diabetes and miRNA-770-5p knockdown protects pancreatic ß-cell function via targeting BAG5 expression.

MicroRNA (miR)-770-5p expression is increased in patients with type 2 diabetes mellitus (T2DM) compared with healthy controls; however, the roles and molecular mechanism underlying miR-770-5p in T2DM are not completely understood. In the present study, the reverse transcription-quantitative PCR (RT-qPCR) results indicated that miR-770-5p expression was significantly increased and Bcl-2 associated athanogene 5 (BAG5) expression was significantly decreased in the serum of patients with T2DM compared with healthy volunteers. TargetScan and a dual luciferase reporter gene system were used to predict and verify BAG5 as a target gene of miR-770-5p. Additionally, the RT-qPCR results demonstrated that miR-770-5p expression was significantly increased and BAG5 expression was significantly decreased in uric acid (UA)-treated Min6 cells compared with control cells. Min6 cells were transfected with miR-770-5p inhibitor and BAG5-small interfering (si)RNA to alter expression levels. The results indicated that miR-770-5p negatively regulated BAG5. The effect of miR-770-5p knockdown on UA-induced pancreatic ß-cell damage and dysfunction was subsequently assessed. Min6 cells were transfected with miR-770-5p inhibitor or miR-770-5p inhibitor + BAG5-siRNA for 48 h, followed by treatment with or without 5 mg/dl UA for 24 h. Cell viability, apoptosis, apoptosis-related factor expression levels and insulin secretion were assessed. The results demonstrated that UA treatment significantly reduced cell viability, increased cell apoptosis and reduced insulin secretion in Min6 cells compared with the control group. miR-770-5p inhibitor significantly attenuated UA-induced injury and dysfunction of Min6 cells, whereas BAG5 knockdown abolished the protective effects of miR-770-5p inhibitor on UA-damaged Min6 cells. In conclusion, miR-770-5p was highly expressed in the serum of patients with T2DM compared with healthy volunteers. In UA-treated pancreatic ß-cells, compared with the inhibitor control group, miR-770-5p knockdown regulated the expression of apoptosis-related genes, increased cell viability, inhibited cell apoptosis and increased insulin secretion by targeting BAG5. Therefore, the present study suggested that miR-770-5p inhibitor may serve a protective role in T2DM.

Down-regulation of lncRNA SNHG5 relieves sepsis-induced acute kidney injury by regulating the miR-374a-3p/TLR4/NF-κB pathway.

Sepsis is an acute systemic infectious disease engendered by infectious factors, which can cause the dysfunction of multiple organs, including acute kidney injury (AKI). Recently, more and more researchers are focussing on long noncoding RNA (lncRNA) that is closely associated with the development and progression of various diseases; however, the role and mechanism of lncRNA in sepsis-induced AKI are not fully understood. Here, we found a significant increase in the expression of lncRNA small nuclear RNA host gene 5 (SNHG5) in the serum of patients with sepsis than healthy controls. Similar results were obtained from mouse model of sepsis. Further investigations revealed that knockdown of SNHG5 improves the viability and reduces the rate of apoptosis and the generation of inflammatory cytokines in HK-2 and TCMK-1 cells treated with lipopolysaccharide. Mechanistically, we showed that SNHG5 can combine with microRNA-374a-3p (miR-374a-3p), which inhibits nuclear factor-κB (NF-κB) activity by targeting TLR4. In conclusion, our results demonstrate that SNHG5 may regulate sepsis-induced AKI via the miR-374a-3p/TLR4/NF-κB pathway, therefore providing a new insight into the treatment of this disease.

Long non­coding RNA CASC2 ameliorates sepsis­induced acute kidney injury by regulating the miR­155 and NF­κB pathway.

Sepsis is a systemic inflammatory response syndrome that can cause multiple­organ damage, including acute kidney injury (AKI). Studies have shown that the long non­coding RNA cancer susceptibility candidate 2 (CASC2) is involved in the occurrence and development of multiple human diseases, although its expression and role in AKI has not yet been reported. The present study demonstrated that the expression of CASC2 was significantly decreased in the serum of patients with sepsis compared with healthy subjects. In addition, the CASC2 level was negatively associated with the severity of AKI. Further experiments revealed that CASC2 promoted cell viability and inhibited inflammatory factor secretion, apoptosis and oxidative stress in lipopolysaccharide­stimulated human renal tubular epithelial HK­2 cells. Importantly, the current study observed that CASC2 was negatively associated with a pro­inflammatory microRNA (miR)­155. In addition, the upregulation of CASC2 significantly suppressed the nuclear factor κB (NF­κB) signaling pathway. In conclusion, the results of the present study suggested that CASC2 may serve as a potential target for treating sepsis­induced AKI by inhibiting the miR­155 and NF­κB pathway­mediated inflammation.

Platelet-derived growth factor B attenuates lethal sepsis through inhibition of inflammatory responses.

Sepsis is a systemic inflammatory response during infection and remains a major clinical problem with high morbidity and mortality. Platelet-derived growth factor B (PDGF-B) is a member belongs to PDGF family and has been recently reported higher expressed in survivors of severe sepsis patients. However, the exact role and underlying mechanisms of PDGF-BB in sepsis remains unclear. In this study, we found that PDGF-BB levels were significantly elevated in patients with sepsis, and higher PDGF-BB levels were negatively correlated with the levels of proinflammatory cytokines (TNF-α, IL-6, IL-1ß, IL-8), and chemokines (CXCL-1 and CCL2). PDGF-BB was also found increased in experimental sepsis in mice. Blockade of PDGF-BB using Tyrphostin AG 1296 aggravated, whereas recombinant PDGF-BB treatment improved survival and tissues injury in both two murine models of CLP-induced sepsis and LPS- induced endotoxemia. PDGF-BB blockade increased, whereas PDGF-BB administration decreased the inflammatory responses, as reflected by proinflammatory cytokines (TNF-α, IL-6, IL-1ß, IL-8), and chemokines (CXCL-1 and CCL2). PDGF-BB also showed inhibitory effect on immune cell activation and cytokines production in vivo and in vitro. Therefore, our findings suggest that PDGF-BB plays a protective role in sepsis by decreasing the production of pro-inflammatory cytokines and chemokines. PDGF-BB thus may be a potential therapeutic strategy for treating sepsis.