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Am J Respir Crit Care Med. 2006 Dec 15;174(12):1327-34. Epub 2006 Sep 28.

Cigarette smoke drives small airway remodeling by induction of growth factors in the airway wall.

Author information

1
Department of Pathology, University of British Columbia, 2211 Wesbrook Mall, Vancouver, BC, Canada V6T 2B5. achurg@interchange.ubc.ca

Abstract

BACKGROUND:

Small airway remodeling (SAR) is an important cause of airflow obstruction in cigarette smokers with chronic obstructive pulmonary disease, but the pathogenesis of SAR is not understood.

OBJECTIVE:

To determine whether smoke causes production of profibrotic growth factors in the airway wall.

METHODS:

We exposed C57Bl/6 mice to cigarette smoke for up to 6 mo and examined growth factor/procollagen gene expression in laser-capture microdissected small airways by real-time reverse transcription-polymerase chain reaction.

RESULTS:

With a single smoke exposure, increases in procollagen, connective tissue growth factor (CTGF), transforming growth factor (TGF)-beta(1), platelet-derived growth factor (PDGF)-A and -B expression were seen 2 h after the start of smoking and declined to baseline by 24 h. With repeated exposures and at killing of animals 24 h after the last exposure, increases in procollagen, CTGF, PDGF-B, and (minimally) PDGF-A expression persisted through 1 wk, 1 mo, and 6 mo. TGF-beta(1) gene expression declined over time; however, increased immunochemical staining for phopho-Smad 2 was present at all time points, indicating continuing TGF-beta downstream signaling. Morphometric analysis showed that the small airways in smoke-exposed mice had more collagen at 6 mo.

CONCLUSIONS:

These findings suggest that smoke can induce growth factor and procollagen production in small airways in a time frame that initially is too short for a significant inflammatory response and that profibrotic growth factor and procollagen gene expression become self-sustaining with repeated smoke exposures. These results imply that the pathogenesis of and possible treatment approaches to emphysema and small airway remodeling might be quite different.

PMID:
17008639
DOI:
10.1164/rccm.200605-585OC
[Indexed for MEDLINE]

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