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Altered fibroblast proteoglycan production in COPD

Hallgren, Oskar LU ; Nihlberg, Kristian LU ; Dahlback, Magnus; Bjermer, Leif LU ; Eriksson, Leif LU ; Erjefält, Jonas LU ; Löfdahl, Claes-Göran LU and Westergren-Thorsson, Gunilla LU (2010) In Respiratory Research 11.
Abstract
Background: Airway remodeling in COPD includes reorganization of the extracellular matrix. Proteoglycans play a crucial role in this process as regulators of the integrity of the extracellular matrix. Altered proteoglycan immunostaining has been demonstrated in COPD lungs and this has been suggested to contribute to the pathogenesis. The major cell type responsible for production and maintenance of ECM constituents, such as proteoglycans, are fibroblasts. Interestingly, it has been proposed that central airways and alveolar lung parenchyma contain distinct fibroblast populations. This study explores the hypothesis that altered depositions of proteoglycans in COPD lungs, and in particular versican and perlecan, is a result of dysregulated... (More)
Background: Airway remodeling in COPD includes reorganization of the extracellular matrix. Proteoglycans play a crucial role in this process as regulators of the integrity of the extracellular matrix. Altered proteoglycan immunostaining has been demonstrated in COPD lungs and this has been suggested to contribute to the pathogenesis. The major cell type responsible for production and maintenance of ECM constituents, such as proteoglycans, are fibroblasts. Interestingly, it has been proposed that central airways and alveolar lung parenchyma contain distinct fibroblast populations. This study explores the hypothesis that altered depositions of proteoglycans in COPD lungs, and in particular versican and perlecan, is a result of dysregulated fibroblast proteoglycan production. Methods: Proliferation, proteoglycan production and the response to TGF-beta(1) were examined in vitro in centrally and distally derived fibroblasts isolated from COPD patients (GOLD stage IV) and from control subjects. Results: Phenotypically different fibroblast populations were identified in central airways and in the lung parenchyma. Versican production was higher in distal fibroblasts from COPD patients than from control subjects (p < 0.01). In addition, perlecan production was lower in centrally derived fibroblasts from COPD patients than from control subjects (p < 0.01). TGF-beta(1) triggered similar increases in proteoglycan production in distally derived fibroblasts from COPD patients and control subjects. In contrast, centrally derived fibroblasts from COPD patients were less responsive to TGF-beta(1) than those from control subjects. Conclusions: The results show that fibroblasts from COPD patients have alterations in proteoglycan production that may contribute to disease development. Distally derived fibroblasts from COPD patients have enhanced production of versican that may have a negative influence on the elastic recoil. In addition, a lower perlecan production in centrally derived fibroblasts from COPD patients may indicate alterations in bronchial basement membrane integrity in severe COPD. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Respiratory Research
volume
11
publisher
BioMed Central
external identifiers
  • wos:000279298600001
  • scopus:77956672918
ISSN
1465-9921
DOI
10.1186/1465-9921-11-55
language
English
LU publication?
yes
id
e87fff87-93fd-4580-bc3f-cbef334e73b9 (old id 1628633)
date added to LUP
2010-07-21 16:17:19
date last changed
2018-07-01 03:18:59
@article{e87fff87-93fd-4580-bc3f-cbef334e73b9,
  abstract     = {Background: Airway remodeling in COPD includes reorganization of the extracellular matrix. Proteoglycans play a crucial role in this process as regulators of the integrity of the extracellular matrix. Altered proteoglycan immunostaining has been demonstrated in COPD lungs and this has been suggested to contribute to the pathogenesis. The major cell type responsible for production and maintenance of ECM constituents, such as proteoglycans, are fibroblasts. Interestingly, it has been proposed that central airways and alveolar lung parenchyma contain distinct fibroblast populations. This study explores the hypothesis that altered depositions of proteoglycans in COPD lungs, and in particular versican and perlecan, is a result of dysregulated fibroblast proteoglycan production. Methods: Proliferation, proteoglycan production and the response to TGF-beta(1) were examined in vitro in centrally and distally derived fibroblasts isolated from COPD patients (GOLD stage IV) and from control subjects. Results: Phenotypically different fibroblast populations were identified in central airways and in the lung parenchyma. Versican production was higher in distal fibroblasts from COPD patients than from control subjects (p &lt; 0.01). In addition, perlecan production was lower in centrally derived fibroblasts from COPD patients than from control subjects (p &lt; 0.01). TGF-beta(1) triggered similar increases in proteoglycan production in distally derived fibroblasts from COPD patients and control subjects. In contrast, centrally derived fibroblasts from COPD patients were less responsive to TGF-beta(1) than those from control subjects. Conclusions: The results show that fibroblasts from COPD patients have alterations in proteoglycan production that may contribute to disease development. Distally derived fibroblasts from COPD patients have enhanced production of versican that may have a negative influence on the elastic recoil. In addition, a lower perlecan production in centrally derived fibroblasts from COPD patients may indicate alterations in bronchial basement membrane integrity in severe COPD.},
  author       = {Hallgren, Oskar and Nihlberg, Kristian and Dahlback, Magnus and Bjermer, Leif and Eriksson, Leif and Erjefält, Jonas and Löfdahl, Claes-Göran and Westergren-Thorsson, Gunilla},
  issn         = {1465-9921},
  language     = {eng},
  publisher    = {BioMed Central},
  series       = {Respiratory Research},
  title        = {Altered fibroblast proteoglycan production in COPD},
  url          = {http://dx.doi.org/10.1186/1465-9921-11-55},
  volume       = {11},
  year         = {2010},
}