Background Inflammatory response mediated by microglia plays a key role in cerebral ischemia-reperfusion injury. This study intends to probe the role of lncRNA SNHG4 in regulating the inflammatory response of the microglia during cerebral ischemia reperfusion. Materials and Methods Blood samples and cerebrospinal fluid samples were collected from acute cerebral infarction (ACI) patients and healthy controls. The middle cerebral artery occlusion (MCAO) models were constructed with rats. LPS induction and oxygen-glucose deprivation methods were respectively applied to simulate the activation of microglia in vitro. qRT-PCR was employed to determine the expressions of SNHG4, miR-449c-5p and related inflammatory factors in vivo and in vitro. The inflammatory responses of the microglia subject to the varied expressions of SNHG4 and miR-449c-5p were detected. Luciferase assays were conducted to verify the crosstalk involving SNHG4, miR-449c-5p and STAT6. Results Compared with the control group, the expression of SNHG4 derived from the samples of ACI patients and the microglia of MCAO group were remarkably down-regulated, but the expression of miR-449c-5p was dramatically up-regulated. Overexpression of SNHG4 and knock-down of miR-449c-5p could inhibit the expression of pro-inflammatory cytokine in the microglia and promote the expression of anti-inflammatory factors. Meanwhile, the phospho-STAT6 was up-regulated, whereas the knock-down of SNHG4 and over-expression of miR-449c-5p in microglia had the opposite effects. Luciferase assay confirmed that SNHG4 could target miR-449c-5p, while miR-449c-5p could target STAT6. Conclusion SNHG4 can regulate STAT6 and repress inflammation by adsorbing miR-449c-5p in microglia during cerebral ischemia-reperfusion injury.

Background/Aims:Acute lung injury (ALI) and its aggressive stage, acute respiratory distress syndrome (ARDS), are characterized by diffuse damage and increased permeability of the endothelial barrier, leading to alveolar infiltrates and interstitial edema. Enhancing endothelial integrity represents a novel therapeutic strategy for ALI/ARDS. Endothelial progenitor cells (EPCs) have been reported to participate in endothelial repair of ALI and also serve as a tool for gene therapy. Further, bone morphogenetic protein 2 (BMP2) is an essential signaling molecule that regulates the fate of different cell types. The aim of our study is to explore whether bone marrow-derived EPCs transduced with lentiviral-mediated BMP2 gene might benefit lipopolysaccharide (LPS)-induced ALI in a rat model. Methods: Rats were divided randomly into five groups. The sham group was given normal saline via the trachea and right jugular vein. The other four groups underwent intratracheal-LPS-induced ALI followed after 30 min by treatment with either normal saline, EPCs, EPCs transduced with empty lentiviral vector (EPCs-null), or EPCs transduced with BMP2 (EPCs-BMP2) via the right jugular vein. Results: We found that the lung injury score, oxygenation, and inflammatory response were significantly ameliorated in the three EPC-treated groups (EPCs, EPCs-null, and EPCs-BMP2). In addition, EPCs-BMP2 further improved endothelium repair and capillary permeability, causing markedly reduced wet-to-dry lung-weight ratio and BALF protein content, and increased levels of BMP2 protein, BMP2 mRNA, and eNOS protein in lung tissues. Conclusion: Transplantation of BMP2-transduced EPCs effectively attenuates edema and protein exudation compared with EPCs alone in LPS-induced ALI via enhanced expression of BMP2 and eNOS.

No abstract

No abstract