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Am J Physiol Lung Cell Mol Physiol. 2014 Dec 15;307(12):L978-86. doi: 10.1152/ajplung.00111.2014. Epub 2014 Oct 24.

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

Author information

1
Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota;
2
Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota;
3
Mayo Medical School, Rochester, Minnesota;
4
Department of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota; and.
5
Department of Pediatrics, University of Leicester, Leicester, United Kingdom.
6
Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, Minnesota; Pabelick.christina@mayo.edu.

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 ([Ca(2+)]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, [Ca(2+)]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.

KEYWORDS:

asthma; collagen; lung development; prematurity

PMID:
25344066
PMCID:
PMC4269688
DOI:
10.1152/ajplung.00111.2014
[Indexed for MEDLINE]
Free PMC Article

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