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MicroRNA‑15a‑5p induces pulmonary artery smooth muscle cell apoptosis in a pulmonary arterial hypertension model via the VEGF/p38/MMP‑2 signaling pathway

  • Authors:
    • Wenmei Zhang
    • Yanna Li
    • Xin Xi
    • Guangfa Zhu
    • Shenghao Wang
    • Yan Liu
    • Man Song
  • View Affiliations / Copyright

    Affiliations: Department of Pulmonary and Critical Care Medicine, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, P.R. China, Department of Obstetrics and Gynecology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, P.R. China, Infectious Diseases, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing 100029, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 461-474
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    Published online on: December 18, 2019
       https://doi.org/10.3892/ijmm.2019.4434
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Abstract

The aim of the present study was to investigate the role of microRNA‑15a‑5p (miR‑15a‑5p) in pulmonary arterial hypertension (PAH) and elucidate the underlying pro‑apoptotic mechanism. Reverse transcription‑quantitative PCR analysis and gene microarray hybridization were used to measure the expression of miR‑15a‑5p in the lung tissues of rats with monocrotaline (MCT)‑induced PAH. Flow cytometry and caspase‑3/9 activity assays were adopted to measure the apoptosis of pulmonary artery smooth muscle cells (PASMCs). The expression of apoptosis‑related proteins was analyzed using western blotting. The results demonstrated that the expression of miR‑15a‑5p was significantly increased in the lung tissues of rats with MCT‑induced PAH. In addition, the overexpression of miR‑15a‑5p reduced PASMC proliferation, induced apoptosis, promoted the activity of caspase‑3/9, induced the protein expression of B‑cell lymphoma 2‑associated X protein (Bax), decreased the expression of B‑cell lymphoma 2 (Bcl‑2), increased inflammation, as indicated by the expression of tumor necrosis factor‑α (TNF)‑α and interleukin (IL)‑1β, IL‑6 and IL‑18, suppressed the protein expression of vascular endothelial growth factor (VEGF), and promoted the protein expression levels of phosphorylated (p)‑p38 mitogen‑activated protein kinase (p38) and matrix metalloproteinase (MMP)‑2 in the PASMCs of rats with MCT‑induced PAH. By contrast, the downregulation of miR‑15a‑5p increased cell proliferation, decreased apoptosis, reduced the activity of caspase‑3/9 and the protein expression of Bax, increased the expression of Bcl‑2, inhibited inflammation (as suggested by the expression of TNF‑α, IL‑1β, IL‑6 and IL‑18), induced the protein expression of VEGF, and suppressed the protein expression of p‑p38 and MMP‑2 in the PASMCs of rats with MCT‑induced PAH. The inhibition of VEGF attenuated the effects of the overexpression of miR‑15a‑5p on the inhibition of cell proliferation, apoptotic rate, caspase‑3/9 activity and protein expression of Bax, and it attenuated the increased inflammation, as indicated by the protein expression of p38 and MMP‑2 in the PASMCs. In conclusion, the data of the present study demonstrated that miR‑15a‑5p induced the apoptosis of PASMCs in an animal model of PAH via the VEGF/p38/MMP‑2 signaling pathway. However, further research is required to fully elucidate the role of miR‑15a‑5p in the development of PAH.
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Copy and paste a formatted citation
Spandidos Publications style
Zhang W, Li Y, Xi X, Zhu G, Wang S, Liu Y and Song M: MicroRNA‑15a‑5p induces pulmonary artery smooth muscle cell apoptosis in a pulmonary arterial hypertension model via the VEGF/p38/MMP‑2 signaling pathway. Int J Mol Med 45: 461-474, 2020.
APA
Zhang, W., Li, Y., Xi, X., Zhu, G., Wang, S., Liu, Y., & Song, M. (2020). MicroRNA‑15a‑5p induces pulmonary artery smooth muscle cell apoptosis in a pulmonary arterial hypertension model via the VEGF/p38/MMP‑2 signaling pathway. International Journal of Molecular Medicine, 45, 461-474. https://doi.org/10.3892/ijmm.2019.4434
MLA
Zhang, W., Li, Y., Xi, X., Zhu, G., Wang, S., Liu, Y., Song, M."MicroRNA‑15a‑5p induces pulmonary artery smooth muscle cell apoptosis in a pulmonary arterial hypertension model via the VEGF/p38/MMP‑2 signaling pathway". International Journal of Molecular Medicine 45.2 (2020): 461-474.
Chicago
Zhang, W., Li, Y., Xi, X., Zhu, G., Wang, S., Liu, Y., Song, M."MicroRNA‑15a‑5p induces pulmonary artery smooth muscle cell apoptosis in a pulmonary arterial hypertension model via the VEGF/p38/MMP‑2 signaling pathway". International Journal of Molecular Medicine 45, no. 2 (2020): 461-474. https://doi.org/10.3892/ijmm.2019.4434
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang W, Li Y, Xi X, Zhu G, Wang S, Liu Y and Song M: MicroRNA‑15a‑5p induces pulmonary artery smooth muscle cell apoptosis in a pulmonary arterial hypertension model via the VEGF/p38/MMP‑2 signaling pathway. Int J Mol Med 45: 461-474, 2020.
APA
Zhang, W., Li, Y., Xi, X., Zhu, G., Wang, S., Liu, Y., & Song, M. (2020). MicroRNA‑15a‑5p induces pulmonary artery smooth muscle cell apoptosis in a pulmonary arterial hypertension model via the VEGF/p38/MMP‑2 signaling pathway. International Journal of Molecular Medicine, 45, 461-474. https://doi.org/10.3892/ijmm.2019.4434
MLA
Zhang, W., Li, Y., Xi, X., Zhu, G., Wang, S., Liu, Y., Song, M."MicroRNA‑15a‑5p induces pulmonary artery smooth muscle cell apoptosis in a pulmonary arterial hypertension model via the VEGF/p38/MMP‑2 signaling pathway". International Journal of Molecular Medicine 45.2 (2020): 461-474.
Chicago
Zhang, W., Li, Y., Xi, X., Zhu, G., Wang, S., Liu, Y., Song, M."MicroRNA‑15a‑5p induces pulmonary artery smooth muscle cell apoptosis in a pulmonary arterial hypertension model via the VEGF/p38/MMP‑2 signaling pathway". International Journal of Molecular Medicine 45, no. 2 (2020): 461-474. https://doi.org/10.3892/ijmm.2019.4434
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