title: Ezrin Regulating the Cytoskeleton Remodeling is Required for Hypoxia-Induced Myofibroblast Proliferation and Migration.
abstract: BACKGROUND
  Hypoxia pulmonary arterial hypertension (HPAH) is a disease of the small vessels characterized by sustained vasoconstriction, thickening of arterial walls, vascular remodeling, and progressive increase in pulmonary vascular resistance, thus leading to right heart failure and finally death. Recent evidence demonstrated that massive pulmonary artery smooth muscle-like cells (PASMLCs) accumulating in the intima might also be developed from the differentiation of pulmonary myofibroblast (PMF) of tunica media. And PMF appeared the phenomenon of the cytoskeleton remodeling. So, it would be important in the clarification of the pivotal factors controlling this cytoskeleton structure change.
  
  
  METHODS
  PMFs were cultured from the normal rats and then divided into three groups and incubated by normal or hypoxic conditions respectively. mRNA level was evaluated by real-time reverse transcription polymerase chain reaction, and protein expression was detected by western blot. Cell proliferation was determined by the MTT and thymidine incorporation assay.
  
  
  RESULTS
  Here, we report that the hypoxia increased the expression levels of ezrin mRNA and protein in PMFs, which might explain that the expression of cytoskeletal proteins (destrin, a1-actin, and a1-tubulin) in PMFs was significantly induced by hypoxia. After inhibiting ezrin in PMFs by siRNA transfection, we found the over-expression of cytoskeletal proteins induced by hypoxia was significantly suppressed at all time-points. Additionally, we found that hypoxia or over-expression of ezrin through adenovirus-mediated ezrin gene transfection significantly increases the proliferation and migration of PMFs, and which could be inverted by the transfection of siRNA.
  
  
  CONCLUSIONS
  These findings suggest that ezrin regulating of aberrant dysregulation of cytoskeletal proteins may be the major cause of PMFs' proliferation and migration under the condition of hypoxia and may, therefore, play a fundamental role in the accumulation of PASMLCs of HPAH.
authors.affiliation: Department of Anesthesia, Southwest Hospital, Third Military Medical University , Chongqing , China ; LBCMCP, CNRS, Université P. Sabatier Toulouse III , Toulouse , France.
authors.forename: Bin
authors.initials: B
authors.lastname: Yi
authors.affiliation: Department of Anesthesia, Southwest Hospital, Third Military Medical University , Chongqing , China.
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Anesthesia, Southwest Hospital, Third Military Medical University , Chongqing , China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of Anesthesia, Southwest Hospital, Third Military Medical University , Chongqing , China.
authors.forename: Jian
authors.initials: J
authors.lastname: Cui
authors.affiliation: Institute of Respiratory Disease, Xinqiao Hospital, Third Military Medical University , Chongqing , China.
authors.forename: Guansong
authors.initials: G
authors.lastname: Wang
authors.affiliation: Institute of Respiratory Disease, Xinqiao Hospital, Third Military Medical University , Chongqing , China.
authors.forename: Guisheng
authors.initials: G
authors.lastname: Qian
authors.affiliation: LBCMCP, CNRS, Université P. Sabatier Toulouse III , Toulouse , France.
authors.forename: Karine
authors.initials: K
authors.lastname: Belguise
authors.affiliation: LBCMCP, CNRS, Université P. Sabatier Toulouse III , Toulouse , France.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Anesthesia, Southwest Hospital, Third Military Medical University , Chongqing , China.
authors.forename: Kaizhi
authors.initials: K
authors.lastname: Lu
keywords: cell proliferation; ezrin; hypoxia; pulmonary artery smooth muscle-like cells; pulmonary myofibroblast; pulmonary vascular remodeling