IL-33-ST2 pathway regulates AECII transdifferentiation by targeting alveolar macrophage in a bronchopulmonary dysplasia mouse model.

Evidence points to the indispensable function of alveolar macrophages (AMs) in normal lung development and tissue homeostasis. However, the importance of AMs in bronchopulmonary dysplasia (BPD) has not been elucidated. Here, we identified a significant role of abnormal AM proliferation and polarization in alveolar dysplasia during BPD, which is closely related to the activation of the IL-33-ST2 pathway. Compared with the control BPD group, AMs depletion partially abolished the epithelialmesenchymal transition process of AECII and alleviated pulmonary differentiation arrest. In addition, IL-33 or ST2 knockdown has protective effects against lung injury after hyperoxia, which is associated with reduced AM polarization and proliferation. The protective effect disappeared following reconstitution of AMs in injured IL-33 knockdown mice, and the differentiation of lung epithelium was blocked again. In conclusion, the IL-33-ST2 pathway regulates AECII transdifferentiation by targeting AMs proliferation and polarization in BPD, which shows a novel strategy for manipulating the IL-33-ST2-AMs axis for the diagnosis and intervention of BPD.

[Dynamic expression and role of SUMO-modified C/EBPα in preterm rats with bronchopulmonary dysplasisa induced by hyperoxia exposure].

OBJECTIVE: To study the expression of SUMO-modified CCAAT enhancer binding protein α (C/EBPα) in preterm rat model of bronchopulmonary dysplasisa (BPD) induced by hyperoxia exposure and its role. METHODS: Eighteen preterm rats were randomly divided into an air group and a hyperoxia group (n=9 each). The model of BPD was prepared in preterm rats exposed to hyperoxia. The rats from the two groups were sacrificed on postnatal days 4, 7 and 14 respectively (3 rats at each time) and lung tissues were harvested. Periodic acid-Schiff (PAS) staining was used to observe the differentiation of rat lung tissues. Ki67 expression was detected by immunohistochemistry. Western blot was used to measure the protein expression of small ubiquitin-related modifier-1(SUMO1) and C/EBPα. A co-immunoprecipitation assay was performed to measure the protein expression of SUMO-modified C/EBPα. RESULTS: Compared with the air group, the hyperoxia group showed a decreased glycogen content in the lung tissue on postnatal day 4, and an increased content on postnatal days 7 and 14. Over the time of hyperoxia exposure, the hyperoxia group showed an increased expression of Ki67 in the lung tissue compared with the air group at all time points. Compared with the air group, the protein expression of C/EBPα increased on postnatal day 4 and decreased on postnatal days 7 and 14 in the hyperoxia group (P<0.05). The hyperoxia group had significantly upregulated expression of SUMO1 and SUMO-modified C/EBPα compared with the air group at all time points (P<0.05). In the hyperoxia group, the protein expression of SUMO-modified C/EBPα was positively correlated with the glycogen content (r=0.529, P<0.05) and the expression of Ki67 (r=0.671, P<0.05). CONCLUSIONS: Hyperoxia may induce over-proliferation and differentiation disorders of alveolar epithelial cells in preterm rat model of BPD, possibly through an increased expression of SUMO-modified C/EBP&alpha.

Expression profile analysis of long non-coding RNA associated with vincristine resistance in colon cancer cells by next-generation sequencing.

Vincristine (VCR) is widely used in tumor treatment. However, long-term use of this drug can make tumor cells resistant to it. Furthermore, the mechanisms underlying resistance development are unclear. The aim of this study was to investigate the long non-coding RNAs (lncRNAs) associated with colon cancer drug resistance using next-generation sequencing. A cDNA library of HCT-8 VCR-resistant colon cancer cell was established through PCR amplification. Using HiSeq 2500 sequencing and bioinformatic methods, we identified lncRNAs showing different expression levels in drug-resistant and non-resistant cells, and constructed expression profiles of the lncRNA differences. The pretreatment of data was quality controlled using FastQC software. Transcription of lncRNA was calculated using Fragments Per Kilobase of transcript per Million fragments mapped (FPKM). To reveal the potential functions of these lncRNAs, we applied GO analysis to study the differentially expressed lncRNAs. Total transcript number was higher in resistant cells than in non-resistant colon cancer cells, and high-quality transcripts constituted the major portion of the total. In addition, 121 transcripts showed significantly different expression in VCR-resistant and non-resistant cells. Of these, we observed 23 up-regulated and 20 down-regulated lncRNAs (fold change >10.0). This is the first report of the expression profile of lncRNA of VCR-resistant colon cancer cells. Abnormal lncRNA expression was associated with VCR resistance in colon cancer cells and these expression differences may play a key role in VCR resistance of these cells.