Abstract
Background and objectiveApoptosis of lung epithelial cell is implicated in the pathogenesis of acute lung injury (ALI). To study the protective effect and mechanism of cancer susceptibility candidate 2 (CASC2) on reducing lung epithelial cell apoptosis after LPS inducing acute lung injury in mice.Methods and resultsThe ALI mice model was performed by intratracheally instilling with lipopolysaccharide (LPS). The CASC2 expression detected by quantitative real-time polymerase chain reaction was significantly decreased in LPS-induced A549 cell and ALI mice model. LPS induced A549 cell apoptosis, while transfection with pcDNA-CASC2 reversed the increased cell apoptosis, suggesting overexpression of CASC2 inhibited LPS-induced A549 cell apoptosis. In addition, we found that miR-144-3p expression were opposite to CASC2, while Aquaporin-1 (AQP1) expression was opposite to miR-144-3p in LPS-induced A549 cell and ALI mice model. The RNA immunoprecipitation and RNA pull-down assay demonstrated that CASC2 could function as a miR-144-3p decoy. The luciferase reporter assay revealed that AQP1 was a target of miR-144-3p in A549 cell. And then, further in vitro studied showed that CASC2 controlled AQP1 expression by regulating miR-144-3p, and LPS induced A549 cell apoptosis by regulating CASC2/miR-144-3p/AQP1 axis. At last, after injection with lentivirus-expressing CASC2 or control lentivirus, the mice were intratracheally instilled with LPS. Comparing to the mice injected with pcDNA, the mice injected with pcDNA-CASC2 had a significantly reduced lung wet–dry weight ratio.ConclusionsLong non-coding RNA CASC2 improved acute lung injury by regulating miR-144-3p/AQP1 axis to reduce lung epithelial cell apoptosis.
Highlights
Background and objectiveApoptosis of lung epithelial cell is implicated in the pathogenesis of acute lung injury (ALI)
Instruction Acute lung injury (ALI) is a life-threatening syndrome that can cause acute hypoxemic respiratory failure, which is characterized by diffuse alveolar damage, increased alveolar capillary membrane permeability, edema, excessive pulmonary inflammation and apoptosis of alveolar epithelial cells [1]
This study raised a question regarding whether miR-144-3p participated in LPS-induced ALI and lung epithelial cells apoptosis by regulating AQP1
Summary
Methods and resultsThe ALI mice model was performed by intratracheally instilling with lipopolysaccharide (LPS). The CASC2 expression detected by quantitative real-time polymerase chain reaction was significantly decreased in LPS-induced A549 cell and ALI mice model. We found that miR-144-3p expression were opposite to CASC2, while Aquaporin-1 (AQP1) expression was opposite to miR-144-3p in LPS-induced A549 cell and ALI mice model. After injection with lentivirus-expressing CASC2 or control lentivirus, the mice were intratracheally instilled with LPS. The ALI mice model was performed by intratracheally instilling with 10 μg LPS in 50 μL of PBS, and the control mice were given an equal volume of PBS. Measurement of wet‐to‐dry ratio of the lungs Thirty minutes before LPS treatment, the BALB/c mice were injected with 100 μL lentivirus-expressing CASC2 or the control lentivirus (MOI = 5 * 107 TU/mL, GeneChem, Shanghai, China) by tail vein, and treated with LPS as described in ALI mice model. The lungs were incubated at 60 °C for 3–4 days to remove all moisture, the dry weight was measured and the ratio of wet-to-dry weight calculated
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