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Enhanced ROCK1 dependent contractility in fibroblast from chronic obstructive pulmonary disease patients

Hallgren, Oskar LU ; Rolandsson Enes, Sara LU orcid ; Andersson Sjöland, Annika LU ; Nihlberg, Kristian LU ; Wieslander, Elisabet LU ; Kvist Reimer, Martina LU ; Dahlback, Magnus ; Eriksson, Leif LU ; Bjermer, Leif LU and Erjefält, Jonas LU , et al. (2012) In Journal of Translational Medicine 10.
Abstract
Background: During wound healing processes fibroblasts account for wound closure by adopting a contractile phenotype. One disease manifestation of COPD is emphysema which is characterized by destruction of alveolar walls and our hypothesis is that fibroblasts in the COPD lungs differentiate into a more contractile phenotype as a response to the deteriorating environment. Methods: Bronchial (central) and parenchymal (distal) fibroblasts were isolated from lung explants from COPD patients (n = 9) (GOLD stage IV) and from biopsies from control subjects and from donor lungs (n = 12). Tissue-derived fibroblasts were assessed for expression of proteins involved in fibroblast contraction by western blotting whereas contraction capacity was... (More)
Background: During wound healing processes fibroblasts account for wound closure by adopting a contractile phenotype. One disease manifestation of COPD is emphysema which is characterized by destruction of alveolar walls and our hypothesis is that fibroblasts in the COPD lungs differentiate into a more contractile phenotype as a response to the deteriorating environment. Methods: Bronchial (central) and parenchymal (distal) fibroblasts were isolated from lung explants from COPD patients (n = 9) (GOLD stage IV) and from biopsies from control subjects and from donor lungs (n = 12). Tissue-derived fibroblasts were assessed for expression of proteins involved in fibroblast contraction by western blotting whereas contraction capacity was measured in three-dimensional collagen gels. Results: The basal expression of rho-associated coiled-coil protein kinase 1 (ROCK1) was increased in both centrally and distally derived fibroblasts from COPD patients compared to fibroblasts from control subjects (p < 0.001) and (p < 0.01), respectively. Distally derived fibroblasts from COPD patients had increased contractile capacity compared to control fibroblasts (p < 0.01). The contraction was dependent on ROCK1 activity as the ROCK inhibitor Y27632 dose-dependently blocked contraction in fibroblasts from COPD patients. ROCK1-positive fibroblasts were also identified by immunohistochemistry in the alveolar parenchyma in lung tissue sections from COPD patients. Conclusions: Distally derived fibroblasts from COPD patients have an enhanced contractile phenotype that is dependent on ROCK1 activity. This feature may be of importance for the elastic dynamics of small airways and the parenchyma in late stages of COPD. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Chronic obstructive pulmonary disease, Contractility, Emphysema, Fibroblast/myofibroblast, Rho-associated coiled-coil protein kinase 1
in
Journal of Translational Medicine
volume
10
publisher
BioMed Central (BMC)
external identifiers
  • wos:000310028100001
  • scopus:84865185558
  • pmid:22913419
ISSN
1479-5876
DOI
10.1186/1479-5876-10-171
language
English
LU publication?
yes
id
cb07b765-c1b1-43d9-87ba-86a3d762d292 (old id 3175140)
date added to LUP
2016-04-01 14:08:19
date last changed
2023-11-13 03:02:46
@article{cb07b765-c1b1-43d9-87ba-86a3d762d292,
  abstract     = {{Background: During wound healing processes fibroblasts account for wound closure by adopting a contractile phenotype. One disease manifestation of COPD is emphysema which is characterized by destruction of alveolar walls and our hypothesis is that fibroblasts in the COPD lungs differentiate into a more contractile phenotype as a response to the deteriorating environment. Methods: Bronchial (central) and parenchymal (distal) fibroblasts were isolated from lung explants from COPD patients (n = 9) (GOLD stage IV) and from biopsies from control subjects and from donor lungs (n = 12). Tissue-derived fibroblasts were assessed for expression of proteins involved in fibroblast contraction by western blotting whereas contraction capacity was measured in three-dimensional collagen gels. Results: The basal expression of rho-associated coiled-coil protein kinase 1 (ROCK1) was increased in both centrally and distally derived fibroblasts from COPD patients compared to fibroblasts from control subjects (p &lt; 0.001) and (p &lt; 0.01), respectively. Distally derived fibroblasts from COPD patients had increased contractile capacity compared to control fibroblasts (p &lt; 0.01). The contraction was dependent on ROCK1 activity as the ROCK inhibitor Y27632 dose-dependently blocked contraction in fibroblasts from COPD patients. ROCK1-positive fibroblasts were also identified by immunohistochemistry in the alveolar parenchyma in lung tissue sections from COPD patients. Conclusions: Distally derived fibroblasts from COPD patients have an enhanced contractile phenotype that is dependent on ROCK1 activity. This feature may be of importance for the elastic dynamics of small airways and the parenchyma in late stages of COPD.}},
  author       = {{Hallgren, Oskar and Rolandsson Enes, Sara and Andersson Sjöland, Annika and Nihlberg, Kristian and Wieslander, Elisabet and Kvist Reimer, Martina and Dahlback, Magnus and Eriksson, Leif and Bjermer, Leif and Erjefält, Jonas and Löfdahl, Claes-Göran and Westergren-Thorsson, Gunilla}},
  issn         = {{1479-5876}},
  keywords     = {{Chronic obstructive pulmonary disease; Contractility; Emphysema; Fibroblast/myofibroblast; Rho-associated coiled-coil protein kinase 1}},
  language     = {{eng}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Journal of Translational Medicine}},
  title        = {{Enhanced ROCK1 dependent contractility in fibroblast from chronic obstructive pulmonary disease patients}},
  url          = {{https://lup.lub.lu.se/search/files/3810920/3735809.pdf}},
  doi          = {{10.1186/1479-5876-10-171}},
  volume       = {{10}},
  year         = {{2012}},
}