title: Identification of downstream target genes regulated by the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate signal pathway in pulmonary hypertension.
abstract: OBJECTIVE
  To investigate the downstream target genes regulated by the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) signal pathway and their possible roles in the pathogenesis of pulmonary hypertension (PH).
  
  
  METHODS
  Digital gene expression tag profiling was performed to identify genes that are differentially expressed after activation of the NO-sGC-cGMP signal pathway in human pulmonary artery smooth muscles cells using 8-bromo-cyclic guanosine monophosphate, BAY 41-2272 and BAY 60-2770. Results were confirmed using real-time polymerase chain reaction. Gene ontology and signal transduction network analyses were also performed.
  
  
  RESULTS
  A number of genes were differentially expressed, including MMP1, SERPINB2, GREM1 and IL8. A total of 68 gene ontology terms and seven pathways were found to be associated with these genes. Most of these genes are involved in cell proliferation, cell migration and apoptosis, which may contribute to the pathological pulmonary vascular remodelling in PH.
  
  
  CONCLUSIONS
  These results may provide new insights into the molecular mechanisms of PH.
authors.affiliation: Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing, China.
authors.forename: Lihui
authors.initials: L
authors.lastname: Zou
authors.affiliation: Department of Respiratory and Critical Care Medicine, Beijing Hospital, Ministry of Health, Beijing, China.
authors.forename: Xiaomao
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Respiratory and Critical Care Medicine, China-Japan Friendship Hospital, Ministry of Health, Beijing, China.
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Zhai
authors.affiliation: Department of Respiratory and Critical Care Medicine, China-Japan Friendship Hospital, Ministry of Health, Beijing, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
authors.affiliation: Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing, China.
authors.forename: Junhua
authors.initials: J
authors.lastname: Jin
authors.affiliation: Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, Beijing, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Xiao
authors.affiliation: Department of Respiratory and Critical Care Medicine, China-Japan Friendship Hospital, Ministry of Health, Beijing, China National Clinical Research Center of Respiratory Medicine, Beijing, China cyh-birm@263.com.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
mesh_terms: D001565:Benzoates / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D020869:Gene Expression Profiling; D063990:Gene Ontology; D006157:Guanosine Monophosphate / Q000378:metabolism*; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D006976:Hypertension, Pulmonary / Q000201:enzymology* / Q000235:genetics*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D011651:Pulmonary Artery / Q000473:pathology; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D000071756:Soluble Guanylyl Cyclase / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: C423582:3-(4-Amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridine; C528797:4-(((4-carboxybutyl) (2- (5-fluoro-2-((4'-(trifluoromethyl) biphenyl-4-yl)methoxy)phenyl)ethyl) amino)methyl)benzoic acid; D001565:Benzoates; D001713:Biphenyl Compounds; D006845:Hydrocarbons, Fluorinated; D011720:Pyrazoles; D011725:Pyridines; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D006157:Guanosine Monophosphate; D000071756:Soluble Guanylyl Cyclase; D006152:Cyclic GMP
keywords: NO-sGC-cGMP pathway; Pulmonary hypertension; differentially expressed genes; digital gene expression tag profiling array; gene ontology; signalling pathway