Cigarette Smoke Drives Small Airway Remodeling by Induction of Growth Factors in the Airway Wall

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)-β1, 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-β1 gene express...