title: Extracellular matrix proteins modulate asthmatic airway smooth muscle cell proliferation via an autocrine mechanism.
abstract: BACKGROUND
  Airway remodeling is a key feature of persistent asthma and includes alterations in the extracellular matrix protein profile around the airway smooth muscle (ASM) and hyperplasia of the ASM. We have previously shown that nonasthmatic ASM cells in culture produce a range of extracellular matrix protein proteins and that asthmatic ASM cells proliferate faster than cells from nonasthmatic patients.
  
  
  OBJECTIVE
  In this study, we compared the profile of extracellular matrix proteins produced by nonasthmatic and asthmatic ASM cells. We also examined the influence of these extracellular matrix protein proteins and conditioned medium derived from nonasthmatic or asthmatic ASM cells on the proliferation of nonasthmatic and asthmatic ASM cells.
  
  
  METHODS
  Extracellular matrix proteins were measured by ELISA; proliferation of ASM cells was measured by tritiated thymidine incorporation.
  
  
  RESULTS
  Production of perlecan and collagen I by the cells from asthmatic patients were significantly increased. In contrast, laminin alpha1 and collagen IV were decreased. Chondroitin sulfate was detectable only in the cells from nonasthmatic patients. Compared with nonasthmatic extracellular matrix proteins, proteins from asthmatic cells enhanced ASM cell proliferation. Conditioned medium from asthmatic ASM cells did not induce greater proliferation compared with conditioned medium from nonasthmatic cells.
  
  
  CONCLUSIONS
  The data show that the profile of extracellular matrix protein components is altered in asthmatic cells and that this altered profile and not soluble mediators secreted from the ASM cells has the potential to influence the proliferation of these cells. These changes are likely to contribute to the airway wall remodeling that occurs in asthma.
authors.affiliation: Department of Pharmacology, University of Sydney, Sydney, NSW 2006, Australia.
authors.forename: Peter R A
authors.initials: PR
authors.lastname: Johnson
authors.forename: Janette K
authors.initials: JK
authors.lastname: Burgess
authors.forename: P Anne
authors.initials: PA
authors.lastname: Underwood
authors.forename: Wendy
authors.initials: W
authors.lastname: Au
authors.forename: Maree H
authors.initials: MH
authors.lastname: Poniris
authors.forename: Michael
authors.initials: M
authors.lastname: Tamm
authors.forename: Qi
authors.initials: Q
authors.lastname: Ge
authors.forename: Michael
authors.initials: M
authors.lastname: Roth
authors.forename: Judith L
authors.initials: JL
authors.lastname: Black
mesh_terms: D000328:Adult; D000368:Aged; D019898:Autocrine Communication; D016022:Case-Control Studies; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005109:Extracellular Matrix; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D012137:Respiratory System / Q000378:metabolism* / Q000473:pathology*
chemical_list: D017077:Culture Media, Conditioned; D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger