title: Functional consequences of human airway smooth muscle phenotype plasticity.
abstract: OBJECTIVE
  Airway smooth muscle (ASM) phenotype plasticity, characterized by reversible switching between contractile and proliferative phenotypes, is considered to contribute to increased ASM mass and airway hyper-responsiveness in asthma. Further, increased expression of collagen I has been observed within the ASM bundle of asthmatics. Previously, we showed that exposure of intact bovine tracheal smooth muscle (BTSM) to collagen I induces a switch from a contractile to a hypocontractile, proliferative phenotype. However, the functional relevance of this finding for intact human ASM has not been established.
  
  
  METHODS
  We investigated the effects of exposure of human tracheal smooth muscle (HTSM) strips to monomeric collagen I and PDGF on contractile responses to methacholine and KCl. Expression of contractile proteins sm-α-actin and sm-MHC was assessed by Western blot analysis. The proliferation of HTSM cells was assessed by cell counting, measuring mitochondrial activity (Alamarblue conversion) and [(3) H]-thymidine incorporation. Proliferation of intact tissue slices was assessed by [(3) H]-thymidine incorporation.
  
  
  RESULTS
  Culturing HTSM strips in the presence of collagen I or PDGF for 4 days reduced maximal contractile responses to methacholine or KCl and the expression of contractile proteins. Conversely, collagen I and PDGF increased proliferation of HTSM cells and proliferative responses in tissue slices. PDGF additively increased the proliferation of HTSM cells cultured on collagen I; this additive effect was not observed on contractility, contractile protein expression or proliferation of intact tissue.
  
  
  CONCLUSIONS
  These findings indicate that collagen I and PDGF induce a functionally hypocontractile, proliferative phenotype of human ASM, which may contribute to airway remodelling in asthma.
authors: Department of Molecular Pharmacology, University of Groningen, Groningen, the Netherlands. b.g.j.dekkers@rug.nl
authors: Bart G J
authors: BG
authors: Dekkers
authors: I Sophie T
authors: IS
authors: Bos
authors: Johan
authors: J
authors: Zaagsma
authors: Herman
authors: H
authors: Meurs
mesh_terms: D000199:Actins / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000494:pharmacology*; D006801:Humans; D016210:Methacholine Chloride / Q000494:pharmacology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism; D010641:Phenotype; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D014132:Trachea / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000199:Actins; D024042:Collagen Type I; D010982:Platelet-Derived Growth Factor; D016210:Methacholine Chloride; D011189:Potassium Chloride; D018995:Myosin Heavy Chains