LncRNA SNHG6 accelerates hyperoxia-induced lung cell injury via regulating miR-335 to activate KLF5/NF-κB pathway.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in premature infants, and its pathogenesis has not been clarified. Long non-coding RNAs (lncRNA) have important functions in cell bioactivity. However, their role in developmental lung disease remains unclear. OBJECTIVE: The aim of this study was to demonstrate the role of lncRNA SNHG6 (SNHG6) in BPD and its underlying mechanisms. METHODS: The blood of patients with BPD were collected, and BPD model of BEAS-2B cells was established by hyperoxia method. SNHG6, miR-335 and KLF5 mRNA expression were detected by RT-qPCR. Western blot was conducted to measure the levels of apoptosis-related proteins' expression and NF-κB pathway related proteins. BEAS-2B cell viability and apoptosis were assessed by CCK-8 and flow cytometry, respectively. Assay Kit was applied to detect ROS, MDA and SOD levels, respectively. ELISA was performed to assess the levels of inflammatory factors. The binding site of miR-335 with SNHG6 or KLF5 were predicted by using DIANA or TargetScan, and which was verified by double luciferase reporter assay. RESULTS: Firstly, SNHG6 was highly expressed and miR-335 was lowly expressed in BPD model, SNHG6 knockdown and miR-335 mimics both alleviated hyperoxia-induced lung cell injury, and SNHG6 targeted miR-335. Subsequently, KLF5 was targeted by miR-335, and KLF5 promoted lung cell injury via activating NF-κB pathway. Furthermore, SNHG6 mediated lung cell injury via regulating the miR-335/KLF5/NF-κB pathway. CONCLUSION: Our research confirmed that SNHG6 mediated hyperoxia-induced lung cell injury via regulating the miR-335/KLF5/NF-κB pathway. These findings suggest that SNHG6 serves as promising targets for the treatment of newborns with BPD.

[Dynamic change in vitamin D level in infants/toddlers with severe pneumonia and a correlation analysis].

OBJECTIVE: To study the correlation of dynamic change in serum 25-hydroxy vitamin D [25(OH)D] level with the disease severity and related laboratory markers in infants/toddlers with severe pneumonia. METHODS: A total of 132 infants/toddlers with severe pneumonia who were hospitalized between March 2017 and March 2018 were enrolled as the severe pneumonia group. According to the disease severity on admission and after one week of treatment, they were further divided into non-critical group (41 children on admission and 78 after one week of treatment), critical group (59 children on admission and 35 after one week of treatment), and extremely critical group (32 children on admission and 19 after one week of treatment). A total of 142 infants/toddlers who underwent physical examination during the same period of time were enrolled as the healthy control group. The serum levels of 25(OH)D, procalcitonin (PCT), and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured on admission and after one week of treatment for the severe pneumonia group, and the serum level of 25(OH)D was measured on admission for the healthy control group. According to the 25(OH)D level after one week of treatment, the children with severe pneumonia were divided into increased vitamin D (VD) group with 81 children and reduced VD group with 51 children, and a comparative analysis and a correlation analysis were performed. RESULTS: The severe pneumonia group had a significantly lower mean 25(OH)D level than the healthy control group (P<0.05), and all the three subgroups of different severities had significantly lower 25(OH)D level than the healthy control group (P<0.05). On admission and after one week of treatment, the non-critical group had a significantly higher 25(OH)D level than the critical and extremely critical groups (P<0.01), and the critical group had a significantly higher 25(OH)D level than the extremely critical group (P<0.05). The extremely critical and critical groups had significantly higher serum levels of PCT and NT-proBNP than the non-critical group on admission and after one week of treatment (P<0.05). After one week of treatment, compared with the reduced VD group, the increased VD group had a significantly less serious condition. At discharge, the increased VD group had a significantly better outcome compared with the reduced VD group (P<0.01). In the children with severe pneumonia, the change value of serum 25(OH)D level after treatment was negatively correlated with the change values of PCT and NT-proBNP (r=-0.597 and -0.404 respectively; P<0.01). CONCLUSIONS: The change in VD level is correlated with the severity of severe pneumonia in infants/toddlers and can be used as an index for disease monitoring. VD supplementation may help with disease recovery.