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Abstract：
Background: Exposure to hyperoxia is an important factor in the development of bronchopulmonary dysplasia (BPD) in preterm newborns. MicroRNAs (miRs) have been implicated in the pathogenesis of BPD and provide a potential therapeutic target. Methods: This study was conducted utilizing a postnatal animal model of experimental hyperoxia-induced murine BPD to investigate the expression and function of miR-195 as well as its molecular signaling targets within developing mouse lung tissue. Results: miR-195 expression levels increased in response to hyperoxia in male and female lungs, with the most significant elevation occurring in 40% O2 (mild) and 60% O2 (moderate) BPD. The inhibition of miR-195 improved pulmonary morphology in the hyperoxia-induced BPD model in male and female mice with females showing more resistance to injury and better recovery of alveolar chord length, septal thickness, and radial alveolar count. Additionally, we reveal miR-195-dependent signaling pathways involved in BPD and identify PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2) as a novel specific target protein of miR-195. Conclusions: Our data demonstrate that high levels of miR-195 in neonatal lungs cause the exacerbation of hyperoxia-induced experimental BPD while its inhibition results in amelioration. This finding suggests a therapeutic potential of miR-195 inhibition in preventing BPD.
摘要：
背景：高氧暴露是早产儿支气管肺发育不良（BPD）发展的重要因素。MicroRNAs（miRs）与BPD的发病机制有关，并提供了潜在的治疗靶标。方法：这项研究是利用实验性高氧诱导的鼠BPD的出生后动物模型进行的，以研究miR-195的表达和功能以及其在发育中的小鼠肺组织中的分子信号传导靶标。结果：miR-195表达水平在男性和女性肺部高氧反应中增加，最明显的升高发生在40％O2（轻度）和60％O2（中度）BPD中。miR-195的抑制改善了高氧诱导的BPD模型中雄性和雌性小鼠的肺形态，雌性小鼠表现出更高的损伤抗性和更好的肺泡弦长度恢复。间隔厚度,和放射状肺泡计数。此外,我们揭示了参与BPD的miR-195依赖性信号通路,并鉴定了富含PH结构域亮氨酸的重复蛋白磷酸酶2(PHLPP2)作为miR-195的新的特异性靶蛋白.结论：我们的数据表明，新生儿肺中高水平的miR-195导致高氧诱导的实验性BPD恶化，而其抑制导致改善。这一发现表明miR-195抑制在预防BPD中的治疗潜力。
