title: Urokinase-type plasminogen activator receptor interaction with β1 integrin is required for platelet-derived growth factor-AB-induced human mesenchymal stem/stromal cell migration.
abstract: BACKGROUND
  Mesenchymal stem cells (MSC) are well described for their role in tissue regeneration following injury. Migratory properties of endogenous or administrated MSC are critical for tissue repair processes. Platelet-derived growth factor (PDGF) is a chemotactic growth factor that elicits mesenchymal cell migration. However, it is yet to be elucidated if signaling pathways other than direct activation of PDGF receptor (PDGF-R) are involved in PDGF-induced cell migration.
  
  
  METHODS
  Knocking down and co-immunoprecipitation approaches were used to evaluate urokinase-type plasminogen activator receptor (uPAR) requirement and its interactions with proteins involved in migration mechanisms, in human MSC induced to migrate under PDGF-AB effect.
  
  
  RESULTS
  We demonstrated that uPAR activation and its association with β1-integrin are required for PDGF-AB-induced migration. This phenomenon takes place in MSC derived from bone marrow and from adipose tissue.
  
  
  CONCLUSIONS
  We showed that PDGF-AB downstream signaling requires other effector molecules in MSC such as the uPA/uPAR system and β1 integrin signaling pathway known for their role in migration. These findings provide new insights in molecular mechanisms of PDGF-AB-induced migration of human MSC that may be relevant to control MSC function and tissue remodeling after injury.
authors.affiliation: EFS Centre-Atlantique, BP 40661, 37 206, Tours, Cedex 3, France. valerie.chabot@efs.sante.fr.
authors.forename: Valérie
authors.initials: V
authors.lastname: Chabot
authors.affiliation: CNRS UMR5273 STROMALab, BP 84225, F-31 432, Toulouse, Cedex 4, France. cecile.berthezene@inserm.fr.|Université Paul Sabatier de Toulouse, BP 84225, F-31 432, Toulouse, Cedex 4, France. cecile.berthezene@inserm.fr.|INSERM U1031, BP 84225, F-31 432, Toulouse, Cedex 4, France. cecile.berthezene@inserm.fr.|EFS Pyrénées -Méditerranée BP 84225, F-31 432, Toulouse, Cedex 4, France. cecile.berthezene@inserm.fr.
authors.forename: Cécile
authors.initials: C
authors.lastname: Dromard
authors.affiliation: EFS Centre-Atlantique, BP 40661, 37 206, Tours, Cedex 3, France. angelique.rico@efs.sante.fr.
authors.forename: Angélique
authors.initials: A
authors.lastname: Rico
authors.affiliation: EFS Centre-Atlantique, BP 40661, 37 206, Tours, Cedex 3, France. alain.langonne@efs.sante.fr.
authors.forename: Alain
authors.initials: A
authors.lastname: Langonné
authors.affiliation: EFS Centre-Atlantique, BP 40661, 37 206, Tours, Cedex 3, France. julien.gaillard@univ-tours.fr.|Département des Microscopies, Faculté de Médecine, 37 032, Tours, Cedex, France. julien.gaillard@univ-tours.fr.
authors.forename: Julien
authors.initials: J
authors.lastname: Gaillard
authors.affiliation: CNRS UMR5273 STROMALab, BP 84225, F-31 432, Toulouse, Cedex 4, France. fabien.guilloton@efs.sante.fr.|Université Paul Sabatier de Toulouse, BP 84225, F-31 432, Toulouse, Cedex 4, France. fabien.guilloton@efs.sante.fr.|INSERM U1031, BP 84225, F-31 432, Toulouse, Cedex 4, France. fabien.guilloton@efs.sante.fr.|EFS Pyrénées -Méditerranée BP 84225, F-31 432, Toulouse, Cedex 4, France. fabien.guilloton@efs.sante.fr.
authors.forename: Fabien
authors.initials: F
authors.lastname: Guilloton
authors.affiliation: CNRS UMR5273 STROMALab, BP 84225, F-31 432, Toulouse, Cedex 4, France. louis.casteilla@inserm.fr.|Université Paul Sabatier de Toulouse, BP 84225, F-31 432, Toulouse, Cedex 4, France. louis.casteilla@inserm.fr.|INSERM U1031, BP 84225, F-31 432, Toulouse, Cedex 4, France. louis.casteilla@inserm.fr.|EFS Pyrénées -Méditerranée BP 84225, F-31 432, Toulouse, Cedex 4, France. louis.casteilla@inserm.fr.
authors.forename: Louis
authors.initials: L
authors.lastname: Casteilla
authors.affiliation: CNRS UMR5273 STROMALab, BP 84225, F-31 432, Toulouse, Cedex 4, France. luc.sensebe@efs.sante.fr.|Université Paul Sabatier de Toulouse, BP 84225, F-31 432, Toulouse, Cedex 4, France. luc.sensebe@efs.sante.fr.|INSERM U1031, BP 84225, F-31 432, Toulouse, Cedex 4, France. luc.sensebe@efs.sante.fr.|EFS Pyrénées -Méditerranée BP 84225, F-31 432, Toulouse, Cedex 4, France. luc.sensebe@efs.sante.fr.
authors.forename: Luc
authors.initials: L
authors.lastname: Sensebé
mesh_terms: D002465:Cell Movement; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator / Q000378:metabolism*; D015398:Signal Transduction; D019096:Vitronectin / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D005353:Fibronectins; D019012:Integrin beta1; D010982:Platelet-Derived Growth Factor; D055293:Receptors, Urokinase Plasminogen Activator; D019096:Vitronectin; C095477:platelet-derived growth factor AB