Cigarette smoke enhances proliferation and extracellular matrix deposition by human fetal airway smooth muscle

Elizabeth R. Vogel, Sarah K. Vanoosten, Michelle A. Holman, Danielle D. Hohbein, Michael A. Thompson, Robert Vassallo, Hitesh C. Pandya, Y. S. Prakash, Christina M. Pabelick

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Cigarette smoke is a common environmental insult associated with increased risk of developing airway diseases such as wheezing and asthma in neonates and children. In adults, asthma involves airway remodeling characterized by increased airway smooth muscle (ASM) cell proliferation and increased extracellular matrix (ECM) deposition, as well as airway hyperreactivity. The effects of cigarette smoke on remodeling and contractility in the developing airway are not well-elucidated. In this study, we used canalicular-stage (18-20 wk gestational age) human fetal airway smooth muscle (fASM) cells as an in vitro model of the immature airway. fASM cells were exposed to cigarette smoke extract (CSE; 0.5-1.5% for 24-72 h), and cell proliferation, ECM deposition, and intracellular calcium ([Ca2+]i) responses to agonist ?(histamine 10 μM) were used to evaluate effects on remodeling and hyperreactivity. CSE significantly increased cell proliferation and deposition of ECM molecules collagen I, collagen III, and fibronectin. In contrast, [Ca2+]i) responses were not significantly affected by CSE. Analysis of key signaling pathways demonstrated significant increase in extracellular signal-related kinase (ERK) and p38 activation with CSE. Inhibition of ERK or p38 signaling prevented CSE-mediated changes in proliferation, whereas only ERK inhibition attenuated the CSE-mediated increase in ECM deposition. Overall, these results demonstrate that cigarette smoke may enhance remodeling in developing human ASM through hyperplasia and ECM production, thus contributing to development of neonatal and pediatric airway disease.

Original languageEnglish (US)
Pages (from-to)L978-L986
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume307
Issue number12
DOIs
StatePublished - Dec 15 2014

Keywords

  • Asthma
  • Collagen
  • Lung development
  • Prematurity

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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