长链非编码 RNA H19 在高氧诱导的新生支气管肺发育不良小鼠肺损伤中的调控机制。

Mechanism of lncRNA H19 in Regulating Pulmonary Injury in Hyperoxia-Induced Bronchopulmonary Dysplasia Newborn Mice.

机构信息

Department of Pediatrics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People's Republic of China.

Department of Hand and Foot Surgery, Nanchang Fifth Hospital, Nanchang, Jiangxi, People's Republic of China.

出版信息

Am J Perinatol. 2022 Jul;39(10):1089-1096. doi: 10.1055/s-0040-1721498. Epub 2020 Dec 7.

DOI:10.1055/s-0040-1721498

PMID:33285606

Abstract

OBJECTIVE

Bronchopulmonary dysplasia (BPD) is a pulmonary injury related to inflammation and is a major cause of premature infant death. Long noncoding RNAs (lncRNAs) are important regulators in pulmonary injury and inflammation. We investigated the molecular mechanism of lncRNA H19 in pulmonary injury and inflammation in hyperoxia (Hyp)-induced BPD mice.

STUDY DESIGN

The BPD newborn mouse model was established and intervened with H19 to evaluate the pathologic conditions and radial alveolar count (RAC) in lung tissues of mice in the room air (RA) and Hyp group on the 4th, 7th, and 14th days after birth. The levels of BPD-related biomarkers vascular endothelial growth factor (VEGF), transforming growth factor β1 (TGF-β1), and surfactant protein C (SPC) in lung tissues were detected on the 14th day after birth. The expression of and relationships among H19 and miR-17, miR-17, and STAT3 were detected and verified. Levels of interleukin (IL)-6, IL-1β, p-STAT3, and STAT3 levels in mouse lung tissues were detected on the 14th day after birth.

RESULTS

Hyp-induced mice showed increased alveolar diameter, septum, and hyperemia and inflammatory cell infiltration, upregulated H19, decreased overall number and significantly reduced RAC on the 7th and 14th days after birth, which were reversed in the si-H19-treated mice. VEGF was upregulated and TGF-β1 and SPC was decreased in si-H19-treated mice. Moreover, H19 competitively bound to miR-17 to upregulate STAT3. IL-6 and IL-1β expressions and p-STAT3 and STAT3 levels were downregulated after inhibition of H19.

CONCLUSION

Downregulated lncRNA H19 relieved pulmonary injury via targeting miR-17 to downregulate STAT3 and reduced inflammatory response caused by p-STAT3 in BPD newborn mice.

KEY POINTS

· lncRNA H19 was highly expressed in Hyp-induced BPD newborn mice.. · si-H19 relieved pulmonary injury in Hyp-induced BPD newborn mice.. · si-H19 upregulated miR-17 and downregulated STAT3 expression..

摘要

目的

支气管肺发育不良（BPD）是一种与炎症相关的肺损伤，是导致早产儿死亡的主要原因。长链非编码 RNA（lncRNA）是肺损伤和炎症中的重要调节因子。我们研究了 lncRNA H19 在高氧（Hyp）诱导的 BPD 小鼠肺损伤和炎症中的分子机制。

研究设计

建立 BPD 新生小鼠模型，并通过 H19 干预，评估出生后第 4、7 和 14 天 RA 和 Hyp 组小鼠肺组织的病理情况和肺泡计数（RAC）。出生后第 14 天检测肺组织中与 BPD 相关的生物标志物血管内皮生长因子（VEGF）、转化生长因子β1（TGF-β1）和表面活性蛋白 C（SPC）的水平。检测并验证 H19 与 miR-17、miR-17 和 STAT3 之间的表达和关系。出生后第 14 天检测小鼠肺组织中白细胞介素（IL）-6、IL-1β、p-STAT3 和 STAT3 水平。

结果

Hyp 诱导的小鼠肺泡直径、隔室和充血增加，炎症细胞浸润增加，出生后第 7 和 14 天 H19 上调，整体数量减少，RAC 明显减少，si-H19 处理的小鼠则相反。VEGF 上调，si-H19 处理的小鼠 TGF-β1 和 SPC 减少。此外，H19 竞争性结合 miR-17 以上调 STAT3。抑制 H19 后，IL-6 和 IL-1β 表达以及 p-STAT3 和 STAT3 水平降低。