Hyperoxia-induced miR-342-5p down-regulation exacerbates neonatal bronchopulmonary dysplasia via the Raf1 regulator Spred3

作者全名："Wen, Xin; Zhang, Hui; Xiang, Bo; Zhang, Weiyu; Gong, Fang; Li, Shiling; Chen, Hongyan; Luo, Xuan; Deng, Juan; You, Yaoyao; Hu, Zhangxue; Jiang, Changke"

作者地址："[Jiang, Changke] Chongqing Yongchuan Dist Matern Child Hlth Care H, Dept Pediat, 198 Renming Rd, Chongqing 402160, Peoples R China; [Hu, Zhangxue] Army Med Univ, Dept Pediat, Army Med Ctr, Chongqing, Peoples R China; [Wen, Xin; Zhang, Hui; Xiang, Bo; Gong, Fang; Li, Shiling; Chen, Hongyan; Luo, Xuan; Deng, Juan; You, Yaoyao; Jiang, Changke] Chongqing Med Univ, Yongchuan Hosp, Dept Pediat, Chongqing, Peoples R China; [Zhang, Weiyu] Chongqing Jiulongpo Dist Matern Child Hlth Care H, Dept Pediat, Chongqing, Peoples R China"

通信作者："Jiang, CK (corresponding author), Chongqing Yongchuan Dist Matern Child Hlth Care H, Dept Pediat, 198 Renming Rd, Chongqing 402160, Peoples R China.; Hu, ZX (corresponding author), Army Med Univ, Dept Pediat, Army Med Ctr, Chongqing, Peoples R China."

来源：BRITISH JOURNAL OF PHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000638257900001

JCR分区：Q1

影响因子：7.3

年份：2021

卷号：178

期号：11

开始页：2266

结束页：2283

文献类型：Article

关键词：BPD; bronchopulmonary dysplasia; hyperoxia; miR‐ 342‐ 5p; Raf1; Spred3

摘要："Background and Purpose Bronchopulmonary dysplasia (BPD) is the most prevalent chronic paediatric lung disease and is linked to the development of chronic obstructive pulmonary disease. MicroRNA-based regulation of type II alveolar epithelial cell (T2AEC) proliferation and apoptosis is an important factor in the pathogenesis of BPD and warrants further investigation. Experimental Approach Two murine models of hyperoxic lung injury (with or without miR-342-5p or Sprouty-related, EVH1 domain-containing protein 3 [Spred3] modulation) were employed: a hyperoxia-induced acute lung injury model (100% O-2 on postnatal days 1-7) and the BPD model (100% O-2 on postnatal days 1-4, followed by room air for 10 days). Tracheal aspirate pellets from healthy control and moderate/severe BPD neonates were randomly selected for clinical miR-342-5p analysis. Key Results Hyperoxia decreased miR-342-5p levels in primary T2AECs, MLE12 cells and neonatal mouse lungs. Transgenic miR-342 overexpression in neonatal mice ameliorated survival rates and improved the BPD phenotype and BPD-associated pulmonary arterial hypertension (PAH). T2AEC-specific miR-342 transgenic overexpression, as well as miR-342-5p mimic therapy, also ameliorated the BPD phenotype and associated PAH. miR-342-5p targets the 3 ' UTR of the Raf1 regulator Spred3, inhibiting Spred3 expression. Treatment with recombinant Spred3 exacerbated the BPD phenotype and associated PAH. Notably, miR-342-5p inhibition under room air conditions did not mimic the BPD phenotype. Moderate/severe BPD tracheal aspirate pellets exhibited decreased miR-342-5p levels relative to healthy control pellets. Conclusion and Implications These findings suggest that miR-342-5p mimic therapy may show promise in the treatment or prevention of BPD."

基金机构：National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81571474]; Medical Scientific Research Program of Chongqing Municipal Healthe Planning Commision [2015MSXM057]

基金资助正文："National Natural Science Foundation of China, Grant/Award Number: 81571474; Medical Scientific Research Program of Chongqing Municipal Healthe Planning Commision in 2015, Grant/Award Number: 2015MSXM057"