Knockdown of miR-203a-3p alleviates the development of bronchopulmonary dysplasia partly via the up-regulation of vascular endothelial growth factor A

Cheng, Hanrong1; Chen, Li2; Wei, Yongli2; Hu, Tianyong3,4; Li, Dongcai3,4; Wu, Benqing5

2021-02-01

10.1007/s10863-020-09863-3

JOURNAL OF BIOENERGETICS AND BIOMEMBRANES   影响因子和分区

0145-479X

1573-6881

Bronchopulmonary dysplasia (BPD) is characterized by impaired vascular and alveolar development, and the underlying molecular mechanisms have remained elusive. MicroRNAs are important players in various biological functions including the pathogenesis of BPD. The present study aimed to examine the expression of miR-203a-3p in the peripheral blood of BPD patients and elucidate the mechanisms underlying miR-203a-3p-mediated progression of BPD. We examined the expression of miR-203a-3p in the peripheral blood of BPD patients and found that miR-203a-3p was up-regulated in the patients. Additionally, the mRNA expression levels of vascular endothelial growth factor A (VEGFA) and hypoxia-inducible factor-1alpha were down-regulated in the BPD patients. Further in vitro studies showed that miR-203a-3p suppressed the expression of VEGFA in RLE-6TN cells by targeting the VEGFA 3 ' untranslated region. Overexpression of miR-203a-3p inhibited the viability of RLE-6TN cells and induced cell apoptosis, whereas the knockdown of miR-203a-3p exerted opposite effects. VEGFA treatment significantly attenuated the increase in the RLE-6TN cell apoptotic rates induced by miR-203a-3p overexpression; while VEGFA knockdown significantly increased the cell apoptotic rates of RLE-6TN cells, which was partially reversed by the treatment with miR-203a-3p inhibitor. Furthermore, miR-203a-3p was up-regulated, whereas VEGFA was down-regulated in the lung tissues of BPD rats, and sequestration of the expression of miR-203a-3p prevented hyperoxia-induced lung damage, increased VEGFA mRNA and protein expression levels, and promoted the protein expression of ERK, PI3K, and p38 in the lung tissues of BDP rats. In summary, the findings of our study indicate that miR-203a-3p knockdown alleviates hyperoxia-induced lung tissue damage in the BPD rat model, and its effect may be associated with the up-regulation of VEGF.

Bronchopulmonary dysplasia Hyperoxia miR-203a-3p VEGFA RLE-6TN Damage

SCI

英语

第一

Biophysics ; Cell Biology

Biophysics ; Cell Biology

WOS:000605884900002

SPRINGER/PLENUM PUBLISHERS

BIOLOGY & BIOCHEMISTRY

Web of Science

1.Southern Univ Sci & Technol, Jinan Univ, Shenzhen Peoples Hosp, Inst Resp Dis,Affiliated Hosp 1,Clin Med Coll 2, Shenzhen 518020, Peoples R China
2.Southern Univ Sci & Technol, Jinan Univ, Shenzhen Peoples Hosp, Inst Pediat,Affiliated Hosp 1,Clin Med Coll 2, Shenzhen 518020, Peoples R China
3.Longgang ENT Hosp, Inst ENT, Shenzhen 518172, Peoples R China
4.Shenzhen Key Lab ENT, Shenzhen 518172, Peoples R China
5.Univ Chinese Acad Sci, Dept Neonatol, Shenzhen Hosp, Shenzhen 518000, Peoples R China

Cheng, Hanrong,Chen, Li,Wei, Yongli,et al. Knockdown of miR-203a-3p alleviates the development of bronchopulmonary dysplasia partly via the up-regulation of vascular endothelial growth factor A[J]. JOURNAL OF BIOENERGETICS AND BIOMEMBRANES,2021,53(1).

Cheng, Hanrong,Chen, Li,Wei, Yongli,Hu, Tianyong,Li, Dongcai,&Wu, Benqing.(2021).Knockdown of miR-203a-3p alleviates the development of bronchopulmonary dysplasia partly via the up-regulation of vascular endothelial growth factor A.JOURNAL OF BIOENERGETICS AND BIOMEMBRANES,53(1).

Cheng, Hanrong,et al."Knockdown of miR-203a-3p alleviates the development of bronchopulmonary dysplasia partly via the up-regulation of vascular endothelial growth factor A".JOURNAL OF BIOENERGETICS AND BIOMEMBRANES 53.1(2021).