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.

中文翻译：

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抑制microRNA-29a通过上调GAB1减轻新生小鼠高氧诱导的支气管肺发育不良

背景支气管肺发育不良（BPD）的主要特征是肺泡简化、肺生长停滞和肺功能异常。多项研究强调了 microRNA-29 (miR-29) 作为肺部疾病和癌症的潜在生物标志物。已知 miR-29a 的上调会下调 GRB2 相关结合蛋白 1 (GAB1)，该蛋白通常在肺中高度表达。目前的研究旨在通过在新生小鼠模型中靶向 GAB1 来研究 miR-29a 在高氧诱导的 BPD 中的潜在作用。方法 使用RT-qPCR和蛋白质印迹分析测定miR-29a和GAB1在高氧诱导的BPD新生小鼠肺组织和小鼠肺泡上皮细胞（MLE-12）中的表达。随后，使用计算机分析验证了 miR-29a 和 GAB1 之间的关系。为了评估 miR-29a 或 GAB1 对 BPD 的影响，通过功能获得和功能丧失研究测量了肺泡的病理特征以及细胞的增殖和凋亡。结果 在 BPD 建模后，肺组织和 MLE-12 细胞中 miR-29a 的上调和 GAB1 的下调都很明显。GAB1 是 miR-29a 的直接靶基因。在高氧诱导的 BPD 建模后，抑制 miR-29a 和过表达 GAB1 可减轻肺损伤，促进细胞增殖和抑制细胞凋亡，但减少新生小鼠肺组织的弦长。结论 总之，miR-29a 的下调可能会提高 GAB1 的表达，减少细胞凋亡并刺激增殖，最终延缓小鼠 BPD 的发展。