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Authors Wang CG, Li C, Lei W, Jiang JH, Huang JA, Zeng DX
Received 16 September 2017
Accepted for publication 11 December 2017
Published 13 April 2018 Volume 2018:13 Pages 1177—1186
DOI https://doi.org/10.2147/COPD.S151820
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Charles Downs
Peer reviewer comments 2
Editor who approved publication: Dr Chunxue Bai
Introduction: Chronic hypoxia-induced pulmonary vascular remodeling is a feature of
chronic obstructive pulmonary disease (COPD). Our previous reports indicate
that neuron-derived orphan receptor 1 (NOR1) promoted pulmonary smooth muscle
cell proliferation in vitro. But it remains unclear whether NOR1 participated
into hypoxia-induced pulmonary vascular remodeling in COPD patients.
Patients and
methods: For this study, we collected
peripheral lung tissues of 26 male COPD patients with or without hypoxemia. We
detected the pulmonary vascular remodeling in all the peripheral lung tissues.
Primary human pulmonary arterial smooth muscle cells were also cultured in
vitro and stimulated with hypoxia or normoxia. Cell proliferation and protein
levels were detected.
Results: COPD patients with hypoxemia showed significantly enlarged
pulmonary vessels wall thickness and increased protein levels of HIF-1α, smooth
muscle actin, cyclin D1, and NOR1 when compared with those in normoxic
patients. Moreover, hypoxia induced human pulmonary arterial smooth muscle cell
proliferation and NOR1 overexpression in vitro. The plasmid-based NOR1 gene
overexpression markedly promoted DNA synthesis and proliferation in hypoxia or
normoxic cells. Human NOR1 gene-specific siRNA intensively suppressed DNA
synthesis and proliferation. Transfection of NOR1 overexpression plasmid raised
cyclin D1 protein levels, which could be significant inhibited by NOR1-specific
siRNA or a CDK4/6 inhibitor PD0332991.
Conclusion: We concluded that NOR1 upregulation is associated with
hypoxia-induced pulmonary vascular remodeling in COPD via promoting human
pulmonary arterial smooth muscle cell proliferation.
Keywords: pulmonary arterial smooth muscle cells, neuron-derived orphan
receptor 1, cyclin D1, hypoxia, pulmonary vascular remodelling