Expression and regulatory mechanism of miR-34a in neonatal rat model of bron-chopulmonary dysplasia induced by hyperoxia

  • Mengyue HUO ,
  • Hua MEI ,
  • Yuheng ZHANG ,
  • Yanbo ZHANG ,
  • Chunli LIU
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  • Department of Neonatology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010050, China
MEI Hua, e-mail, meihuayani@sina.com

Received date: 2022-03-22

  Online published: 2025-04-12

Supported by

the Natural Science Foundation of Inner Mongolia Autonomous Region Project(2020MS08034);the Major Scientific Research Project of Inner Mongolia Medical University Affiliated Hospital(NYFY ZD008)

Copyright

, 2025, All rights reserved. Unauthorized reproduction is prohibited.

Abstract

Objective: To investigate the expression and possible regulatory mechanism of miR-34a in the lung tissue of neonatal rat model of bronchopulmonary dysplasia (BPD) induced by hyperoxia. Methods: In the study, 80 newborn SD rats were randomly divided into hyperoxia group (FiO2=60%) and air group (FiO2=21%) within 2 hours after birth, 40 rats per group. Lung tissue samples of the SD rats in each group were extracted on the 1st, 7th, 14th and 21st days after birth, and the pathological changes of lung tissue were observed under light microscope after HE staining. The number of radial alveolar counts (RAC) and the mean alveolar diameter (MAD) and the thickness of alveolar septal thickness (AST) were measured to evaluate the development of alveoli. Real-time fluorescence quantitative PCR was used to detect the expression of miR-34a, angiopoietin-1 (Ang-1) and tyrosine kinase receptor-2 (Tie-2) in lung tissue of rats in hyperoxia group and air group at different time points. Enzyme-linked immunosorbent assay (ELISA) was used to detect the proteins expression of Ang-1 and Tie-2 in the lung tissues of the two groups at different time points. Results: The weight of rats in the hyperoxia group on the 7th, 14th and 21st days after birth was significantly lower than that in the air group (P all < 0.05). With the prolongation of oxygen exposure, the number of alveoli decreased, the volume increased, the structure simplified, the alveolar cavity enlarged obviously and the alveolar septum thickened in the hyperoxia group. On the 7th, 14th and 21st days after birth, the RAC in the hyperoxia group was significantly lower than that in the air group (P all < 0.05). Compared with the air group, MAD and AST increased significantly on the 7th, 14th and 21st days after birth in the hyperoxia group, and the difference was statistically significant (P all < 0.05). The expression level of miR-34a in lung tissue of hyperoxia group was significantly higher than that of air group on the 7th, 14th and 21st days after birth, and the difference was statistically significant (P all < 0.05). Compared with the air group at the same time point, the expression levels of Ang-1 and Tie-2 mRNA and protein in the hyperoxia group were lower than those in the air group on the 14th and 21st days after birth (P all < 0.05). Conclusion: The new BPD model of newborn SD rats can be successfully established by continuous exposure to 60% hyperoxia. The expression of miR-34a was up-regulated in the lung tissue of the new BPD model of neonatal rats. MiR-34a may play an important role in the occurrence and development of BPD by regulating Ang-1/Tie-2 signal pathway.

Cite this article

Mengyue HUO , Hua MEI , Yuheng ZHANG , Yanbo ZHANG , Chunli LIU . Expression and regulatory mechanism of miR-34a in neonatal rat model of bron-chopulmonary dysplasia induced by hyperoxia[J]. Journal of Peking University(Health Sciences), 2025 , 57(2) : 237 -244 . DOI: 10.19723/j.issn.1671-167X.2025.02.003

References

1 Jensen EA , Edwards EM , Greenberg LT , et al. severity of bronchopulmonary dysplasia among very preterm infants in the United States[J]. Pediatrics, 2021, 148 (1): e2020030007.
2 Ronkainen E , Perhomaa M , Mattila L , et al. Structural pulmonary abnormalities still evident in schoolchildren with new bronchopulmonary dysplasia[J]. Neonatology, 2018, 113 (2): 122- 130.
3 Dang MN , Gomez Casas C , Day ES , et al. Photoresponsive miR-34a/nanoshell conjugates enable light-triggered gene regulation to impair the function of triple-negative breast cancer cells[J]. Nano Lett, 2021, 21 (1): 68- 76.
4 Bhaskaran M , Xi D , Wang Y , et al. Idenfification of microRNAs changed in the neonatal lungs in response to hyperoxia exposure[J]. Physiol Genomics, 2012, 44 (20): 970- 980.
5 Kim DH , Kim HS . Serial changes of serum endostatin and angiopoietin-1 levels in preterm infants with severe bronchopulmonary dysplasia and subsequent pulmonary arteryhypertension[J]. Neonatolog, 2014, 106 (1): 55- 61.
6 Dumpa V , Nielsen L , Wang H , et al. Caffeine is associated with improved alveolarization and angiogenesis in malemice following hyperoxia induced lung injury[J]. BMC Pulm Med, 2019, 19 (1): 138.
7 Syed M , Das P , Pawar A , et al. Hyperoxia causes miR-34a-mediated injury via angiopoietin-1 in neonatal lungs[J]. Nat Commun, 2017, 8 (1): 1173.
8 冯洁, 邓春, 余加林, 等. 高迁移率族蛋白B1在高氧致支气管肺发育不良的表达[J]. 中国当代儿科杂志, 2010, 12 (3): 219- 223.
9 Braun RK , Chetty C , Balasubramaniam V , et al. Intraperitoneal injection of MSC-derived exosomes prevent experimental bronc-hopulmonary dysplasia[J]. Biochem Biophys Res Commun, 2018, 503 (4): 2653- 2658.
10 Mei Y , Chen C , Dong H , et al. treatment of hyperoxia-induced lung injury with lung mesenchymal stem cells in mice[J]. Stem Cells Int, 2018, 2018, 5976519.
11 Porzionato A , Guidolin D , Macchi V , et al. Fractal analysis of alveolarization in hyperoxia-induced rat models of bronchopulmonary dysplasia[J]. Am J Physiol Lung Cell Mol Physiol, 2016, 310 (7): L680- L688.
12 Li J , Yu KH , Oehlert J , et al. Exome sequencing of neonatal blood spots and the identification of genes implicated in bron-chopulmonary dysplasia[J]. Am J Respir Crit Care Med, 2015, 192 (5): 589- 596.
13 Alam MA , Betal SGN , Aghai ZH , et al. Hyperoxia causes miR199a-5p-mediated injury in the developing lung[J]. Pediatr Res, 2019, 85 (5): 579- 588.
14 张潇月, 蔡成, 楚晓云, 等. 高体积分数氧暴露对早产新生大鼠肺组织微小RNA-125b、肿瘤坏死因子-α和白细胞介素6表达的影响[J]. 中华实用儿科临床杂志, 2019, 34 (16): 1244- 1248.
15 月小飞, 梅花, 宋丹, 等. 高氧诱导支气管肺发育不良模型新生大鼠肺组织中miR-21-5p的表达[J]. 中国医科大学学报, 2020, 49 (7): 624-627, 635.
16 孙祎璠, 马俐, 龚小慧, 等. 基于生物信息学分析microRNA-495-5p在早产儿支气管肺发育不良中的表达及其临床意义[J]. 中国当代儿科杂志, 2020, 22 (1): 24- 30.
17 van den Berge M , Tasena H . Role of microRNAs and exosomes in asthma[J]. Curr Opin Pulm Med, 2019, 25 (1): 87- 93.
18 Das P , Syed MA , Shah D , et al. miR34a: A master regulator in the pathogenesis of bronchopulmonary dysplasia[J]. Cell Stress, 2018, 2 (2): 34- 36.
19 Ruiz-Camp J , Quantius J , Lignelli E , et al. Targeting miR-34a/Pdgfra interactions partially corrects alveologenesis in experimental bronchopulmonary dysplasia[J]. EMBO Mol Med, 2019, 11 (3): e9448.
20 Liu H , Li S , Xu Y , et al. Engeletin protects against cerebral ischemia/reperfusion injury by modulating the VEGF/vasohibin and Ang-1/Tie-2 pathways[J]. Braz J Med Biol Res, 2021, 54 (10): e11028.
21 王玲, 吕回, 李美雪. 血管生成素-1在高氧诱导新生鼠支气管肺发育不良的表达及与肺发育的关系[J]. 临床儿科杂志, 2014 (4): 355- 359.
22 Sudhadevi T , Jafri A , Ha AW , et al. Hyperoxia-induced S1P signaling reduced angiogenesis by suppression of Tie-2 leading to experimental bronchopulmonary dysplasia[J]. Cell Biochem Biophys, 2021, 79 (3): 561- 573.
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