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. 2012;7(6):e39736.
doi: 10.1371/journal.pone.0039736. Epub 2012 Jun 29.

Vessel-associated transforming growth factor-beta1 (TGF-β1) is increased in the bronchial reticular basement membrane in COPD and normal smokers

Amir Soltani  1 , Sukhwinder Singh Sohal, David Reid, Steve Weston, Richard Wood-Baker, E Haydn Walters
Affiliations

Vessel-associated transforming growth factor-beta1 (TGF-β1) is increased in the bronchial reticular basement membrane in COPD and normal smokers

Amir Soltani et al. PLoS One. 2012.

Abstract

Background: Transforming growth factor-beta1 (TGF-β1) is a multipotential cytokine with angiogenic activity. There are only limited data about its role in airway remodeling in COPD. We have previously shown that the reticular basement membrane (Rbm) is hypervascular in the airways of current smokers either with or without chronic obstructive pulmonary disease (COPD). This study evaluated TGF-β1 immunostaining in the Rbm and its relationship to vascularity in smokers with or without COPD.

Methodology/principal findings: Bronchial biopsies from 15 smokers with normal lung function, 19 current and 14 ex-smokers with COPD were immunostained for TGF-β1 antibody and compared to 17 healthy controls. The percentage area of tissue and also number and area of vessels staining positively for TGF-β1 were measured and compared between groups. Some bronchial biopsies from current smoking COPD subjects were also stained for phosphorylated (active) Smad2/3. Epithelial TGF- β1 staining was not different between COPD current smokers and normal controls. TGF-β1 stained vessels in the Rbm were increased in smokers with normal lung function, current smoking COPD and ex-smokers with COPD compared to controls [median (range) for number of vessels/mm Rbm 2.5 (0.0-12.7), 3.4 (0.0-8.1) and 1.0 (0.0-6.3) vs. 0.0 (0.0-7.0), p<0.05]. Percentage of vessels stained was also increased in these clinical groups. Preliminary data suggest that in current smoking COPD subjects endothelial cells and cells in the Rbm stain positively for phosphorylated Smad2/3 suggesting TGF-β1 is functionally active in this situation.

Conclusions/significance: Vessel-associated TGF-β1 activity is increased in the bronchial Rbm in smokers and especially those with COPD.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Vessels in the airway reticular basement membrane (Rbm) stained for transforming growth factor-beta1 (TGF-β1).
The reticular basement membrane is indicated by a star beneath the epithelium (EP). Vessels in the Rbm are indicated by arrows. Current smoking COPD subject, X400, Scale  = 20 µm.
Figure 2
Figure 2. Number of vessels stained for transforming growth factor-beta1 (TGF-β1) in the reticular basement membrane (Rbm).
Number of vessels are compared in healthy nonsmokers (H-N), smokers with normal lung function (S-N), current smoking COPD (S-COPD) and ex-smokers with COPD (ES-COPD).
Figure 3
Figure 3. The percentage of vessels stained for transforming growth factor-beta1 (TGF-β1).
The percentage is compared in healthy nonsmokers (H-N), smokers with normal lung function (S-N), current smoking COPD (S-COPD) and ex-smokers with COPD (ES-COPD). This ratio is calculated by division of the number of vessels stained for TGF-β1 by the total number of vessels in the reticular basement membrane (Rbm) marked with anti-Collagen IV antibody in serial sections, which we assessed in our previous study (Soltani A. et al., Respiratory Research. 2010, 30;11∶105). Variation in total number of vessels between sections gives occasionally anomalous data-points greater than 100%. The number of subjects in this plot is different from Figure 3 because some individuals did not have enough tissue to provide adequate consecutive sections for both types of immunostaining.
Figure 4
Figure 4. Phosphorylated (activated) Smad2/3 (pSmad2/3) staining of bronchial biopsies in normal nonsmoking controls (A) and current smoking COPD subjects (B).
Black arrows indicate vessels stained with pSmad2/3 in the bronchial Rbm in current smoking COPD. There are very few vessels at all in the Rbm in normals and those that are there do not stain for pSmad2/3. X 400.
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