title: Neuron-derived orphan receptor 1 promoted human pulmonary artery smooth muscle cells proliferation.
abstract: OBJECTIVE
  As a transcription factor of the nuclear receptor superfamily, neuron-derived orphan receptor 1 (NOR1) is induced rapidly in response to various extracellular stimuli. But, it is still unclear its role in pulmonary artery smooth muscle cells proliferation.
  
  
  METHODS
  Human PASMCs were cultured in vitro and stimulated by serum. The special antisense oligodeoxynucleotides (AS-ODNs) were used to knockdown human NOR1 gene expression. Real-time PCR and Western-blot were used to evaluate the gene expression and protein levels.
  
  
  RESULTS
  Fetal bovine serum (FBS) induced human PASMCs proliferation in a dose dependent manner. Furthermore, FBS promoted NOR1 gene expression in a dose dependent manner and a time dependent manner. 10% FBS induced a maximal NOR1 mRNA levels at 2 h. FBS also induced a significant higher NOR1 protein levels as compared with control. The NOR1 over-expressed plasmid significantly promoted DNA synthesis and cells proliferation. Moreover, the special AS-ODNs against human NOR1 not only prevented NOR1 expression but also inhibited DNA synthesis and cells proliferation significantly. The NOR1 over-expression plasmid could up-regulate cyclin D1 expression markedly, but the AS-ODNs inhibited cyclin D1 expression significantly.
  
  
  CONCLUSIONS
  So, we concluded that NOR1 could promote human PASMCs proliferation. Cyclin D1 might be involved in this process.
authors.affiliation: 1Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China.
authors.forename: Chang-Guo
authors.initials: CG
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Lei
authors.forename: Chang
authors.initials: C
authors.lastname: Li
authors.forename: Da-Xiong
authors.initials: DX
authors.lastname: Zeng
authors.forename: Jian-An
authors.initials: JA
authors.lastname: Huang
mesh_terms: D049109:Cell Proliferation; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000378:metabolism; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism*; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
chemical_list: C530104:CCND1 protein, human; D004268:DNA-Binding Proteins; C490412:NR4A3 protein, human; D016376:Oligonucleotides, Antisense; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D019938:Cyclin D1
keywords: Cyclin D1; neuron-derived orphan receptor 1 (NOR1); pulmonary arterial smooth muscle cells (PASMCs); pulmonary hypertension