Fibroblast heterogeneity in the diseased lung
K. Heinzelmann, G. Preissler, H. Winter, R. Hatz, I. Koch, M. Lindner, J. Behr, O. Eickelberg (Munich, Gauting, Germany)
Source: International Congress 2014 – ILDs 3
Session: ILDs 3
Session type: Thematic Poster Session
Number: 788
Disease area: Interstitial lung diseases
Abstract Chronic lung diseases (CLD), such as chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis (IPF), are characterized by altered cellular composition and activation, as well as extracellular matrix (ECM) remodeling. Fibroblasts are thought to be the main ECM producing cell type in the lung. In this study, we hypothesized that different mesenchymal subpopulations within the human lung exhibit different surface marker profiles, and which might respond differentially to TGFbeta - a central key player in IPF and COPD.Primary human fibroblasts were isolated from human lung parenchyma (n=5), taken in culture and treated with TGFbeta or left untreated for 48 hours. Western Blot (WB) and FACS analysis was performed to determine changes on the protein level and in the percentage of cells for ECM components and surface markers such as fibronectin, type I collagen, desmin, PDGFRa , CD90/Thy-1 and HMMR.In FACS analysis 97% (±1.5) of fibroblasts were CD90/Thy-1 positive, whereas 57% (±12.8) were positive for fibronectin, 65% (±12.2) for type I collagen, 48% (±4.2) for desmin, 16% (±15.5) for PDGFRa and 7% (±5.8) for HMMR. After stimulating with TGFbeta, no changes on the protein level or in the percentage of cells could be detected for desmin (44% ±13.0) and CD90 (96% ±3.0), whereas a decrease could be observed for PDGFRa (0% ±0) as well as for HMMR (1% ±0.9), and an increase for fibronectin (80% ±8.0) and type I collagen (83% ±5.4). Similar results could be detected by WB.In sum, we document that different subpopulations exist within the human lung, and which respond differentially to the growth factor TGFbeta in their marker expression. This indicates that different fibroblast subtypes play distinct roles in COPD or IPF.
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K. Heinzelmann, G. Preissler, H. Winter, R. Hatz, I. Koch, M. Lindner, J. Behr, O. Eickelberg (Munich, Gauting, Germany). Fibroblast heterogeneity in the diseased lung. Eur Respir J 2014; 44: Suppl. 58, 788
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