title: Slit2-N inhibits PDGF-induced migration in rat airway smooth muscle cells: WASP and Arp2/3 involved.
abstract: BACKGROUND
  Slit2 has been reported to be implicated in many kinds of cell migration. However little is known about the effect of Slit2 on airway smooth muscle cell migration. This study was to detect the expression of Slit2 in rat airway smooth muscle (RASM) cells stimulated by platelet-derived growth factor (PDGF) and characterized the effect of Slit2-N on PDGF-induced migration of RASM cells in vitro.
  
  
  METHODS
  mRNAs of Slit-Robo in RASM cells were examined by RT-PCR, and the effect of exogenous Slit2-N at different doses on PDGF-induced migration of RASM cells were examined by transwell and scrape-wound assays. Actin filaments (F-actin) were stained with rhodamine-conjugated phalloidin and the levels of protein expression were detected by western blot.
  
  
  RESULTS
  RASM cells were identified to express Slit2, Slit3, Robo1, Robo2 and Robo4 in vitro. Slit2-N caused a time- and dose-dependent inhibition of cell proliferation, while had no significantly effect on cell apoptosis. Slit2-N pretreatment attenuated the elongated morphologic characteristics, reduced lamellipodia formation, inhibited actin rearrangement and cell migration induced by PDGF. PDGF-induced increase of WASP and Arp2/3 proteins were dramatically inhibited by 100 ng/ml Slit2-N.
  
  
  CONCLUSIONS
  Slit2-N inhibits RASM cells migration at least partly through attenuating the expressions of WASP and Arp2/3, inhibiting actin rearrangement in vitro. The results contribute to provide new insights into the pathogenesis of airway remodeling in asthma and may be helpful for development of effective treatments.
authors.affiliation: Department of Respiratory Medicine, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Yangpu District, Shanghai 200433, PR China.
authors.forename: Yunye
authors.initials: Y
authors.lastname: Ning
authors.forename: Qinying
authors.initials: Q
authors.lastname: Sun
authors.forename: Yuchao
authors.initials: Y
authors.lastname: Dong
authors.forename: Wujian
authors.initials: W
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Haidong
authors.initials: H
authors.lastname: Huang
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology*; D051376:Actin-Related Protein 2-3 Complex / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D000077214:Becaplermin; D015153:Blotting, Western; D002352:Carrier Proteins / Q000502:physiology*; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D003598:Cytoskeletal Proteins; D005434:Flow Cytometry; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008297:Male; D008856:Microscopy, Fluorescence; D009130:Muscle, Smooth / Q000166:cytology* / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000077214:Becaplermin; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein; C491670:Wipf1 protein, rat