Dataset Information

Reduction of microRNA-206 contributes to the development of bronchopulmonary dysplasia through up-regulation of fibronectin 1.

ABSTRACT:

Objective

To characterize microRNA-206 (miR-206) in the development of bronchopulmonary dysplasia (BPD).

Design/methods

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.

Results

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.

Conclusions

The expression of miR-206 and its target gene, fn 1, may contribute to the progression of BPD.

SUBMITTER: Zhang X

PROVIDER: S-EPMC3769311 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Reduction of microRNA-206 contributes to the development of bronchopulmonary dysplasia through up-regulation of fibronectin 1.

Zhang Xiaoying X Xu Jing J Wang Junjie J Gortner Ludwig L Zhang Sheng S Wei Xiujuan X Song Jie J Zhang Yupei Y Li Qiuping Q Feng Zhichun Z

PloS one 20130910 9

<h4>Objective</h4>To characterize microRNA-206 (miR-206) in the development of bronchopulmonary dysplasia (BPD).<h4>Design/methods</h4>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 b ...[more]

PMID: 24040336

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Project description:Premature infants are at high risk for developing bronchopulmonary dysplasia (BPD), characterized by chronic inflammation and inhibition of lung development, which we have recently identified as being modulated by microRNAs (miRNAs) and alterations in the airway microbiome. Exosomes and exosomal miRNAs may regulate cell differentiation and tissue and organ development. We discovered that tracheal aspirates from infants with severe BPD had increased numbers of, but smaller, exosomes compared with term controls. Similarly, bronchoalveolar lavage fluid from hyperoxia-exposed mice (an animal model of BPD) and supernatants from hyperoxia-exposed human bronchial epithelial cells (in vitro model of BPD) had increased exosomes compared with air controls. Next, in a prospective cohort study of tracheal aspirates obtained at birth from extremely preterm infants, utilizing independent discovery and validation cohorts, we identified unbiased exosomal miRNA signatures predictive of severe BPD. The strongest signal of reduced miR-876-3p in BPD-susceptible compared with BPD-resistant infants was confirmed in the animal model and in vitro models of BPD. In addition, based on our recent discovery of increased Proteobacteria in the airway microbiome being associated with BPD, we developed potentially novel in vivo and in vitro models for BPD combining Proteobacterial LPS and hyperoxia exposure. Addition of LPS led to a larger reduction in exosomal miR 876-3p in both hyperoxia and normoxia compared with hyperoxia alone, thus indicating a potential mechanism by which alterations in microbiota can suppress miR 876-3p. Gain of function of miR 876-3p improved the alveolar architecture in the in vivo BPD model, demonstrating a causal link between miR 876-3p and BPD. In summary, we provide evidence for the strong predictive biomarker potential of miR 876-3p in severe BPD. We also provide insights on the pathogenesis of neonatal lung disease, as modulated by hyperoxia and microbial product-induced changes in exosomal miRNA 876-3p, which could be targeted for future therapeutic development.

Dataset Information

Reduction of microRNA-206 contributes to the development of bronchopulmonary dysplasia through up-regulation of fibronectin 1.

Objective

Design/methods

Results

Conclusions

Publications

Reduction of microRNA-206 contributes to the development of bronchopulmonary dysplasia through up-regulation of fibronectin 1.

Similar Datasets

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