title: Shear stress regulates late EPC differentiation via mechanosensitive molecule-mediated cytoskeletal rearrangement.
abstract: BACKGROUND
  Previous studies have demonstrated that endothelial progenitor cells (EPCs), in particular late EPCs, play important roles in endothelial maintenance and repair. Recent evidence has revealed shear stress as a key regulator for EPC differentiation. However, the underlying mechanisms regulating the shear stress-induced EPC differentiation have not been understood completely. The present study was undertaken to further investigate the effects of shear stress on the late EPC differentiation, and to elucidate the signal mechanism involved.
  
  
  RESULTS
  In vitro and in vivo assays revealed that cytoskeletal remodeling was involved in the shear stress-upregulated expression of endothelial markers vWF and CD31 in late EPCs, with subsequently increased in vivo reendothelialization after arterial injury. Moreover, shear stress activated several mechanosensitive molecules including integrin β1, Ras, ERK1/2, paxillin and FAK, which were all involved in both cytoskeletal rearrangement and cell differentiation in response to shear stress in late EPCs.
  
  
  CONCLUSIONS
  Shear stress is a key regulator for late EPC differentiation into endothelial cells, which is important for vascular repair, and the cytoskeletal rearrangement mediated by the activation of the cascade of integrin β1, Ras, ERK1/2, paxillin and FAK is crucial in this process.
authors.affiliation: Medicine Research Center, Weifang Medical University, Weifang, Shandong, P R China. chengmin1976@wfmc.edu.cn
authors.forename: Min
authors.initials: M
authors.lastname: Cheng
authors.forename: Xiumei
authors.initials: X
authors.lastname: Guan
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Cui
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Xu
authors.initials: X
authors.lastname: Jing
authors.forename: Haiyan
authors.initials: H
authors.lastname: Wu
authors.forename: Emil
authors.initials: E
authors.lastname: Avsar
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002448:Cell Adhesion; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism; D040542:Mechanotransduction, Cellular / Q000235:genetics*; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D015689:Oncogene Protein p21(ras) / Q000235:genetics / Q000378:metabolism; D051419:Paxillin / Q000235:genetics / Q000378:metabolism; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013314:Stress, Mechanical; D014841:von Willebrand Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D019012:Integrin beta1; D051419:Paxillin; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D014841:von Willebrand Factor; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D015689:Oncogene Protein p21(ras)