title: Moderate hyperoxia induces extracellular matrix remodeling by human fetal airway smooth muscle cells.
abstract: Premature infants are at increased risk for airway diseases, such as wheezing and asthma, because of early exposure to risk factors including hyperoxia. As in adult asthma, airway remodeling and increased extracellular matrix (ECM) deposition is involved.
  
  
  
  We assessed the impact of 24-72 h of moderate hyperoxia (50%) on human fetal airway smooth muscle (fASM) ECM deposition through western blot, modified in-cell western, and zymography techniques.
  
  
  
  Hyperoxia exposure significantly increased collagen I and collagen III deposition, increased pro- and cleaved matrix metalloproteinase 9 (MMP9) activity, and decreased endogenous MMP inhibitor, TIMP1, expression. Hyperoxia-induced change in caveolin-1 (CAV1) expression was assessed as a potential mechanism for the changes in ECM deposition. CAV1 expression was decreased following hyperoxia. Supplementation of CAV1 activity with caveolar scaffolding domain (CSD) peptide abrogated the hyperoxia-mediated ECM changes.
  
  
  
  These results demonstrate that moderate hyperoxia enhances ECM deposition in developing airways by altering the balance between MMPs and their inhibitors (TIMPs), and by increasing collagen deposition. These effects are partly mediated by a hyperoxia-induced decrease in CAV1 expression. In conjunction with prior data demonstrating increased fASM proliferation with hyperoxia, these data further demonstrate that hyperoxia is an important instigator of remodeling in developing airways.
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota.|Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Vogel
authors.affiliation: Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota.
authors.forename: Rodney D
authors.initials: RD
authors.lastname: Britt
authors.affiliation: Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Arij
authors.initials: A
authors.lastname: Faksh
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Ine
authors.initials: I
authors.lastname: Kuipers
authors.affiliation: Department of Pediatrics, University of Leicester, Leicester, UK.
authors.forename: Hitesh
authors.initials: H
authors.lastname: Pandya
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota.|Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota.
authors.forename: Y S
authors.initials: YS
authors.lastname: Prakash
authors.affiliation: Department of Pediatrics, Division of Neonatology, Rainbow-Babies Children's Hospital, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Martin
authors.affiliation: Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota.|Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Pabelick
mesh_terms: D056151:Airway Remodeling; D001249:Asthma / Q000628:therapy; D051242:Caveolin 1 / Q000378:metabolism; D015687:Cell Hypoxia; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009130:Muscle, Smooth / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D010641:Phenotype; D034741:RNA, Small Interfering / Q000378:metabolism; D012137:Respiratory System / Q000187:drug effects / Q000196:embryology*; D012307:Risk Factors; D015398:Signal Transduction; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
chemical_list: C495540:CAV1 protein, human; D051242:Caveolin 1; D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; D034741:RNA, Small Interfering; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9