Journal Article

Inhibition of microRNA-29a alleviates hyperoxia-induced bronchopulmonary dysplasia in neonatal mice via upregulation of GAB1

Fu, Hongling, Xie, Liang, Liu, Hanmin, Yu, Jing, Zhou, Dan, Hu, Yu

2019

Overview

Background The main features of bronchopulmonary dysplasia (BPD) are alveolar simplification, pulmonary growth arrest, and abnormal lung function. Multiple studies have highlighted microRNA-29 (miR-29) as a potential biomarker for lung diseases and cancers. Upregulation of miR-29a has been known to downregulate GRB2-associated-binding protein 1 (GAB1), which is often highly expressed in the lung. The current study was designed to investigate the potential role of miR-29a in hyperoxia-induced BPD by targeting GAB1 in a neonatal mouse model. Methods The expression of miR-29a and GAB1 in lung tissues of neonatal mice with hyperoxia-induced BPD and mouse alveolar epithelial cells (MLE-12) was determined using RT-qPCR and western blot analysis. Subsequently, the relationship between miR-29a and GAB1 was verified using in silico analysis. In order to assess the effects of miR-29a or GAB1 on BPD, the pathological characteristics of alveoli, as well as proliferation and apoptosis of cells were measured through gain- and loss-of-function studies. Results Upregulation of miR-29a and downregulation of GAB1 were evident in both lung tissues and MLE-12 cells following BPD modeling. GAB1 was a direct target gene of miR-29a. Inhibition of miR-29a and overexpression of GAB1 were shown to alleviate lung injury, promote cell proliferation and inhibit apoptosis but reduce chord length in lung tissues of neonatal mice following hyperoxia-induced BPD modeling. Conclusion Altogether, down-regulation of miR-29a can potentially elevate GAB1 expression, reducing cell apoptosis and stimulating proliferation, ultimately retarding the development of BPD in mice. This study highlights the potential of a promising new target for preventing BPD.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Adenoviruses / Apoptosis / Biomedical and Life Sciences / Biomedicine / Bronchopulmonary dysplasia / GAB1 / Hyperoxia / Laboratory animals / Lung cancer / Lung diseases / MicroRNA-29a / MicroRNAs / MLE-12 / Molecular Medicine / Polyclonal antibodies / Premature birth / Research Article / Rodents