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

A Rosendahl, E Pardali, M Speletas… - American journal of …, 2002 - atsjournals.org
A Rosendahl, E Pardali, M Speletas, P Ten Dijke, CH Heldin, P Sideras
American journal of respiratory cell and molecular biology, 2002atsjournals.org
Bone morphogenetic proteins (BMPs) are pleiotropic secreted proteins, structurally related
to transforming growth factor (TGF)-β 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 …
Bone morphogenetic proteins (BMPs) are pleiotropic secreted proteins, structurally related to transforming growth factor (TGF)-β 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 BMP5 and BMP7. Collectively, our 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.
ATS Journals