Lung parenchyma of 14 day old mice.

<p>Sections were stained with toluidine blue. a) Control lungs (No/No) exhibit well developed formed septa, alveoli and ductus alveolares. b) Prenatal hypoxia induced lungs (Hypo/No) show lung parenchyma without clearly visible alterations compared to controls. c) Postnatal hyperoxia induced lungs (No/Hyper) indicate more expanded airspaces with fewer septa than controls. d) Lungs exposed to prenatal hypoxia and postnatal hyperoxia (Hypo/Hyper) display enlarged parenchymal airspaces surrounded by more or less thick septa.</p

Ultrastructure of Alveolar Epithelial cells type II (AEII).

<p>a) Control lungs (No/No) showed AEII with numerous lamellar bodies of different size with more or less densely packed lipid lamellae and mitochondria with a dark matrix and densely packed cristae. b) After prenatal hypoxia (Hypo/No), in AEII normal distribution of subcellular components was seen. The partial loss of lipid lamellae in the Lb may be caused by longer fixation in aldehydes. c) After postnatal hyperoxia (No/Hyper) AEII exhibit numerous mitochondria and Lb without clearly visible differences compared to controls. d) After prenatal hypoxia and postnatal hyperoxia (Hypo/Hyper) AEII contain well preserved mitochondria and Lb with fixation-dependent partial loss of lamellae. Some smaller Lb sections are visible.</p

Total volumes given in percent of controls.

<p>Total volumes given in percent of controls.</p

Design of experimental procedure.

<p>No/No = normoxic control group (FiO₂ = 0.21); Hypo/No = prenatal hypoxia (FiO₂ = 0.10) and postnatal normoxia; No/Hyper = prenatal normoxia and postnatal hyperoxia (FiO₂ = 0.75); Hypo/Hyper = prenatal hypoxia and postnatal hyperoxia.</p

The relative frequencies of the distribution of Lb volume.

<p>The volume weighted mean volume was divided into 15 classes from the smallest to the largest volume. A pronounced shift to Lb with smaller volume was evaluated in the double hit group.</p

The volume weighted mean volume of airspaces.

<p>In controls (normoxia group, No/No), after prenatal hypoxia and postnatal normoxia (Hypo/No group), after prenatal normoxia and postnatal hyperoxia (No/Hyper group) and after prenatal hypoxia and postnatal hyperoxia (Hypo/Hyper group). *p<0.05 compared to controls.</p

Stereological parameters, that characterize lung parenchyma.

<p>Controls (normoxia group, No/No), prenatal hypoxia and postnatal normoxia (Hypo/No group), prenatal normoxia and postnatal hyperoxia ((No/Hyper group) and prenatal hypoxia and postnatal hyperoxia (Hypo/Hyper group). Mean ± SD, *p<0.05, **p<0.01, ***p<0.001 compared to controls. a) The volume densities of airspaces are comparable in all groups. The greatest variation was found in the Hypo/Hyper group. b) The volume densities of alveolar septa are comparable in all groups. The greatest variation was found in the Hypo/Hyper group. c) The septal surface density was significantly reduced in both Hyperoxia groups. d) The mean wall thickness of septa shows a tendency to significance after prenatal hypoxia and postnatal hyperoxia. The values of the other groups are comparable.</p

Stereological parameters characterizing Alveolar Epithelial cells type II (AEII) and lamellar bodies (Lb).

<p>Controls (normoxia group, No/No), after prenatal hypoxia and postnatal normoxia (Hypo/No group), after prenatal normoxia and postnatal hyperoxia ((No/Hyper group) and after prenatal hypoxia and postnatal hyperoxia (Hypo/Hyper group). Mean ± SD, *p<0.05, **p<0.01, ***p<0.001 compared to controls. a) The volume density of AEII showed a more or less pronounced variance in all groups. b) The volume weighted mean volume of AEII showed the significantly highest values compared to controls in the double hit model. c) Volume densities of Lb show comparable values in the one hit models, but significantly lower values in the Hypo/Hyper group. d) The volume weighted mean volume of Lb is comparable with control values in the Hypo/No and in the No/Hyper group. Significantly lower values were found in the double hit group.</p

Reduction of MicroRNA-206 Contributes to the Development of Bronchopulmonary Dysplasia through Up-Regulation of Fibronectin 1

<div><p>Objective</p><p>To characterize microRNA-206 (miR-206) in the development of bronchopulmonary dysplasia (BPD).</p> <p>Design/Methods</p><p>We assessed the expression of miR-206 in BPD mouse lung tissues and blood samples of BPD patients by quantitative real-time PCR. Then, the role of miR-206 in regulating cell biology were examined by XTT assay, flow cytometry, transwell invasion assay, wound healing assay and adhesion assay in vitro. Furthermore, luciferase reporter assay, real-time PCR, western blot and Immunofluorescence staining were performed to figure out the target gene of miR-206.</p> <p>Results</p><p>A reduction in expression of miR-206 was observed in BPD mice compared with controls and in BPD patients compared with controls. miR-206 overexpression significantly induced cell apoptosis, reduced cell proliferation, migration and adhesion abilities, whereas the inhibition of miR-206 expression had the opposite effect. Fibronectin 1 (FN1) is a direct target of miR-206, and fn 1 can be transcriptionally and translationally regulated by miR-206. Down-regulation of miR-206 modulates biological functions of the cells, at least in part, by increasing the level of fn 1. Furthermore, fn 1 expression levels were increased in the BPD mice and BPD patients.</p> <p>Conclusions</p><p>The expression of miR-206 and its target gene, fn 1, may contribute to the progression of BPD.</p> </div

Down-regulated miR-206 involved in the enhanced invasion capability is elicited by FN 1.

<p>(A) Determination of miR-206 and <i>adr 3</i> involvement in A549 cells invasion by the transwell invasion assay. (B) Determination of miR-206 and <i>adr 3</i> involvement in A549 cells adhesion by the adhesion assay. AS, antisense.</p