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Activation of bone morphogenetic protein/Smad signaling in bronchial epithelial cells during airway inflammation

Rosendahl, Ann LU ; Pardali, E; Speletas, M; ten Dijke, P; Heldin, CH and Sideras, P (2002) In American Journal of Respiratory Cell and Molecular Biology 27(2). p.160-169
Abstract
Bone morphogenetic proteins (BMPs) are pleiotropic secreted proteins, structurally related to transforming growth factor (TGF)-beta and activins. BMPs play pivotal roles in the regulation of embryonic lung development and branching of airways and have recently been considered to influence inflammatory processes in adults due to their chemotactic activity on fibroblasts, myocytes, and inflammatory cells. In this study, we have investigated the possible involvement of BMPs in a model of experimental allergic-airway inflammation in situ using antibodies that detect activated Smad proteins, and have monitored the modulation of BMP ligands during the inflammatory response. Inflamed bronchial epithelial cells and a few scattered alveolar cells... (More)
Bone morphogenetic proteins (BMPs) are pleiotropic secreted proteins, structurally related to transforming growth factor (TGF)-beta and activins. BMPs play pivotal roles in the regulation of embryonic lung development and branching of airways and have recently been considered to influence inflammatory processes in adults due to their chemotactic activity on fibroblasts, myocytes, and inflammatory cells. In this study, we have investigated the possible involvement of BMPs in a model of experimental allergic-airway inflammation in situ using antibodies that detect activated Smad proteins, and have monitored the modulation of BMP ligands during the inflammatory response. Inflamed bronchial epithelial cells and a few scattered alveolar cells expressed levels of phosphorylated Smad1 (pSmad1/5), indicative of active BMP/Smad signaling. This was in contrast to healthy epithelium, which was devoid of immunoreactivity. A mechanistic explanation for increased pSmad1/5 staining during inflammation was provided by the upregulated expression of all the BMP type I receptors, i.e., activin receptor-like kinase (ALK)2, ALK3, and ALK6, in the inflamed bronchial epithelial cells. Furthermore, the mRNA and protein profiles for BMP ligands were significantly altered during airway inflammation with induction of BMP2, BMP4, and BMP6, and downregulation of BMPS and BMP7. Collectively, cur data demonstrate for the first time active BMP/Smad signaling during airway inflammation in bronchial epithelial cells and thus raise the possibility that BMPs could play a determining role in respiratory pathophysiology. (Less)
Please use this url to cite or link to this publication:
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organization
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type
Contribution to journal
publication status
published
subject
in
American Journal of Respiratory Cell and Molecular Biology
volume
27
issue
2
pages
160 - 169
publisher
American Thoracic Society
external identifiers
  • wos:000177262200007
  • pmid:12151307
  • scopus:0035984569
ISSN
1535-4989
language
English
LU publication?
yes
id
b72792a9-4c44-482c-b1d7-1fd59282d6fc (old id 332169)
alternative location
http://ajrcmb.atsjournals.org/cgi/reprint/27/2/160.pdf
date added to LUP
2007-11-09 08:56:12
date last changed
2017-08-06 03:37:17
@article{b72792a9-4c44-482c-b1d7-1fd59282d6fc,
  abstract     = {Bone morphogenetic proteins (BMPs) are pleiotropic secreted proteins, structurally related to transforming growth factor (TGF)-beta and activins. BMPs play pivotal roles in the regulation of embryonic lung development and branching of airways and have recently been considered to influence inflammatory processes in adults due to their chemotactic activity on fibroblasts, myocytes, and inflammatory cells. In this study, we have investigated the possible involvement of BMPs in a model of experimental allergic-airway inflammation in situ using antibodies that detect activated Smad proteins, and have monitored the modulation of BMP ligands during the inflammatory response. Inflamed bronchial epithelial cells and a few scattered alveolar cells expressed levels of phosphorylated Smad1 (pSmad1/5), indicative of active BMP/Smad signaling. This was in contrast to healthy epithelium, which was devoid of immunoreactivity. A mechanistic explanation for increased pSmad1/5 staining during inflammation was provided by the upregulated expression of all the BMP type I receptors, i.e., activin receptor-like kinase (ALK)2, ALK3, and ALK6, in the inflamed bronchial epithelial cells. Furthermore, the mRNA and protein profiles for BMP ligands were significantly altered during airway inflammation with induction of BMP2, BMP4, and BMP6, and downregulation of BMPS and BMP7. Collectively, cur data demonstrate for the first time active BMP/Smad signaling during airway inflammation in bronchial epithelial cells and thus raise the possibility that BMPs could play a determining role in respiratory pathophysiology.},
  author       = {Rosendahl, Ann and Pardali, E and Speletas, M and ten Dijke, P and Heldin, CH and Sideras, P},
  issn         = {1535-4989},
  language     = {eng},
  number       = {2},
  pages        = {160--169},
  publisher    = {American Thoracic Society},
  series       = {American Journal of Respiratory Cell and Molecular Biology},
  title        = {Activation of bone morphogenetic protein/Smad signaling in bronchial epithelial cells during airway inflammation},
  volume       = {27},
  year         = {2002},
}