MicroRNA‑431 inhibits the expression of surfactant proteins through the BMP4/activin/TGF‑β signaling pathway by targeting SMAD4

Shen,Yan‑Qing; Bao,Zhi‑Dan; Pan,Jing‑Jing; Mao,Xiao‑Nan; Cheng,Rui; Zhou,Xiao‑Guang; Zhou,Xiao‑Yu; Yang,Yang

doi:10.3892/ijmm.2020.4511

MicroRNA‑431 inhibits the expression of surfactant proteins through the BMP4/activin/TGF‑β signaling pathway by targeting SMAD4

Authors:
- Yan‑Qing Shen
- Zhi‑Dan Bao
- Jing‑Jing Pan
- Xiao‑Nan Mao
- Rui Cheng
- Xiao‑Guang Zhou
- Xiao‑Yu Zhou
- Yang Yang
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Affiliations: Department of Neonates, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu 210008, P.R. China, Department of Pediatrics, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China
Published online on: February 24, 2020 https://doi.org/10.3892/ijmm.2020.4511
Pages: 1571-1582

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Abstract

The synthesis and secretion of surfactant proteins (SPs) is an important sign of lung maturation. Furthermore, the morbidity of lung developmental diseases, including respiratory distress syndrome and bronchopulmonary dysplasia which are mainly caused by immature lung development and lack of SPs, is increasing. As is well known, multiple microRNAs (miRs/miRNAs) are able to influence lung development via numerous different signaling pathways. However, few studies examine the association between the miRNAs and lung developmental diseases. A previous study has demonstrated that miR‑431 was significantly (F=33.49; P<0.001) downregulated in the lung tissues of Sprague‑Dawley rats at 3 time points, embryonic day 19, embryonic day 21 and postnatal day 3. The present study reported that the regulation of miR‑431 may influence the expression of SPs. Thus, the further potential mechanisms of miR‑431 in negatively regulating lung development were examined in the present study. Stable A549 cell lines overexpressing or knocking down SMAD family member 4 (SMAD4) transfected with miR‑431 overexpressed or knocked down, and their control groups were established. Subsequently, the expression of bone morphogenetic protein 4 (BMP4), SMAD4 and SPs (SP‑A, SP‑B and SP‑C) at the RNA and protein levels were validated respectively by reverse transcription quantitative PCR and western blotting. miR‑431 exhibited a decreased expression, while BMP4 and SPs exhibited increased expression at the mRNA and protein levels in the SMAD4 knockdown group. Meanwhile, the expression of SPs were reduced in the SMAD4‑knockdown group via overexpressing miR‑431 and increased in the SMAD4‑overexpression group via inhibiting miR‑431. The present results indicate that SMAD4 negatively regulates the expression of SPs, and that miR‑431 negatively regulates the expression of SPs through inhibiting the BMP4/activin/transforming growth factor‑β signaling pathway by targeting SMAD4.

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