Moderate hyperoxia induces extracellular matrix remodeling by human fetal airway smooth muscle cells

Elizabeth R. Vogel, Rodney Jr. Britt, Arij Faksh, Ine Kuipers, Hitesh Pandya, Y.s. Prakash, Richard J. Martin, Christina M Pabelick

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background: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.Methods: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.Results: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.Conclusion: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.

Original languageEnglish (US)
Pages (from-to)376-383
Number of pages8
JournalPediatric Research
Volume81
Issue number2
DOIs
StatePublished - Feb 1 2017

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Hyperoxia
Smooth Muscle Myocytes
Extracellular Matrix
Caveolin 1
Matrix Metalloproteinase Inhibitors
Collagen
Smooth Muscle
Asthma
Airway Remodeling
Respiratory Sounds
Premature Infants
Western Blotting

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Moderate hyperoxia induces extracellular matrix remodeling by human fetal airway smooth muscle cells. / Vogel, Elizabeth R.; Britt, Rodney Jr.; Faksh, Arij; Kuipers, Ine; Pandya, Hitesh; Prakash, Y.s.; Martin, Richard J.; Pabelick, Christina M.

In: Pediatric Research, Vol. 81, No. 2, 01.02.2017, p. 376-383.

Research output: Contribution to journalArticle

Vogel, Elizabeth R. ; Britt, Rodney Jr. ; Faksh, Arij ; Kuipers, Ine ; Pandya, Hitesh ; Prakash, Y.s. ; Martin, Richard J. ; Pabelick, Christina M. / Moderate hyperoxia induces extracellular matrix remodeling by human fetal airway smooth muscle cells. In: Pediatric Research. 2017 ; Vol. 81, No. 2. pp. 376-383.
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