title: [Role of MEK1/ERK1, 2 pathways in the calcium-sensing receptor mediation of hypoxia-induced proliferation of rat pulmonary artery smooth muscle cells].
abstract: OBJECTIVE
  To explore the cell signal transduction pathway of calcium-sensing receptor (CaSR) mediated hypoxia-induced proliferation of rat pulmonary artery smooth muscle cells (PASMCs).
  
  
  METHODS
  The expressions of proliferating cell nuclear antigen (PCNA) and extracellular signal-regulated protein kinase 1, 2 (ERK1, 2) were analyzed by Western blot. Cell proliferation was tested by a 5-bromo-2-deoxyuridine (BrdU) incorporation assay. Cell cycle and proliferation index (PI) were analyzed by flow cytometry.
  
  
  RESULTS
  Hypoxia significantly increased the expression of PCNA (0.528 ± 0.028), p-ERK1, 2 (1.12 ± 0.05, 0.91 ± 0.06), BrdU incorporation (143.3 ± 4.2) and cell proliferation index (12.5 ± 0.9) (all P < 0.05, versus control group, 0.243 ± 0.025, 0.47 ± 0.03, 0.40 ± 0.03, 100.0 ± 5.4, 7.5 ± 1.2). Gadolinium chloride (GdCl3, a CaSR agonist) amplified the effect of hypoxia (0.770 ± 0.039, 1.50 ± 0.06, 1.61 ± 0.05, 187.4 ± 3.9, 19.8 ± 0.6, all P < 0.05). PD98059 (a MEK1 inhibitor) decreased the up-regulation of PCNA expression, BrdU incorporation and the increase of cell proliferation index induced by hypoxia and GdCl3 in PASMCs (0.441 ± 0.020, 0.71 ± 0.07, 0.72 ± 0.06, 115.5 ± 4.0, 9.3 ± 1.1, all P < 0.05).
  
  
  CONCLUSIONS
  Calcium-sensing receptor mediates hypoxia-induced proliferation of rat pulmonary artery smooth muscle cells through ERK1, 2 pathways.
authors.affiliation: Department of Thoracic and Cardiovascular Disease, First Hospital of Qiqihar, Qiqihar 161005, China.
authors.forename: Hong-zhi
authors.initials: HZ
authors.lastname: Miao
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.forename: Fei-xiang
authors.initials: FX
authors.lastname: Xu
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.forename: Guo-zhong
authors.initials: GZ
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.forename: Zhi-hui
authors.initials: ZH
authors.lastname: Deng
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
authors.forename: Guang-wei
authors.initials: GW
authors.lastname: Li
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D049109:Cell Proliferation; D002478:Cells, Cultured; D048369:MAP Kinase Kinase 1 / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000166:cytology* / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011651:Pulmonary Artery / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048369:MAP Kinase Kinase 1