Altered fibroblast proteoglycan production in COPD.
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-beta1 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-beta1 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-beta1 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.
Hallgren
Oskar
O
Department of Experimental Medical Science, BMC D12 Lund, Lund University, Sweden. oskar.hallgren@med.lu.se
Nihlberg
Kristian
K
Dahlbäck
Magnus
M
Bjermer
Leif
L
Eriksson
Leif T
LT
Erjefält
Jonas S
JS
Löfdahl
Claes-Göran
CG
Westergren-Thorsson
Gunilla
G
D000328:Adult; D000368:Aged; D058578:Biglycan; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D058575:Decorin; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011509:Proteoglycans / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000473:pathology; D012720:Severity of Illness Index; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D053675:Versicans / Q000378:metabolism; D055815:Young Adult
C546884:BGN protein, human; D058578:Biglycan; C546878:DCN protein, human; D058575:Decorin; D016326:Extracellular Matrix Proteins; D019812:Heparan Sulfate Proteoglycans; D011509:Proteoglycans; D053773:Transforming Growth Factor beta1; C508322:VCAN protein, human; D053675:Versicans; C071927:perlecan
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