Activation of bone morphogenetic protein/Smad signaling in bronchial epithelial cells during airway inflammation
(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:
https://lup.lub.lu.se/record/332169
- author
- Rosendahl, A ; Pardali, E LU ; Speletas, M ; ten Dijke, P ; Heldin, CH and Sideras, P
- organization
- publishing date
- 2002
- 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
- 2016-04-01 11:55:29
- date last changed
- 2024-01-08 01:39:37
@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, A 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}},
url = {{http://ajrcmb.atsjournals.org/cgi/reprint/27/2/160.pdf}},
volume = {{27}},
year = {{2002}},
}