miR-4632 mediates PDGF-BB-induced proliferation and antiapoptosis of human pulmonary artery smooth muscle cells via targeting cJUN

Am J Physiol Cell Physiol. 2017 Oct 1;313(4):C380-C391. doi: 10.1152/ajpcell.00061.2017. Epub 2017 Jul 12.


MicroRNAs (miRNAs) can regulate the proliferative status of pulmonary artery smooth muscle cells (PASMCs), which is a core factor modulating pulmonary vascular remodeling diseases, such as atherosclerosis and pulmonary arterial hypertension (PAH). Our previous work has shown that miR-4632, a rarely reported miRNA, is significantly downregulated in platelet-derived growth factor (PDGF)-BB-stimulated human pulmonary artery smooth muscle cells (HPASMCs), yet its cell function and the underlying molecular mechanisms remain to be elucidated. Here, we find that miR-4632 is highly expressed in HPASMCs and its expression significantly decreased in response to different stimuli. Functional studies revealed that miR-4632 inhibited proliferation and promoted apoptosis of HPASMCs but had no effects on cell contraction and migration. Furthermore, the cJUN was identified as a direct target gene of miR-4632, while knockdown of cJUN was necessary for miR-4632-mediated HPASMC proliferation and apoptosis. In addition, the downregulation of miR-4632 by PDGF-BB was found to associate with histone deacetylation through the activation of PDGF receptor/phosphatidylinositol 3'-kinase/histone deacetylase 4 signaling. Finally, the expression of miR-4632 was reduced in the serum of patients with PAH. Overall, our results suggest that miR-4632 plays an important role in regulating HPASMC proliferation and apoptosis by suppression of cJUN, providing a novel therapeutic miRNA candidate for the treatment of pulmonary vascular remodeling diseases. It also implies that serum miR-4632 has the potential to serve as a circulating biomarker for PAH diagnosis.

Keywords: HPASMC; PDGF-BB; cJUN; miRNA; proliferation.

MeSH terms

  • Apoptosis / physiology*
  • Becaplermin
  • Biomarkers / blood
  • Cell Proliferation / physiology*
  • Cell Survival / physiology
  • Cells, Cultured
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • MicroRNAs / metabolism*
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / physiology*
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / physiology*
  • Proto-Oncogene Proteins c-sis / metabolism*
  • Pulmonary Artery / cytology
  • Pulmonary Artery / physiology*


  • Biomarkers
  • MIRN4632 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-sis
  • Becaplermin
  • JNK Mitogen-Activated Protein Kinases