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PMID:12151307

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Citation

Rosendahl, A, Pardali, E, Speletas, M, Ten Dijke, P, Heldin, CH and Sideras, P (2002) Activation of bone morphogenetic protein/Smad signaling in bronchial epithelial cells during airway inflammation. Am. J. Respir. Cell Mol. Biol. 27:160-9

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 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.

Links

PubMed

Keywords

Animals; Bone Morphogenetic Protein Receptors, Type I; Bone Morphogenetic Proteins/genetics; Bone Morphogenetic Proteins/metabolism; DNA-Binding Proteins/metabolism; Disease Models, Animal; Epithelial Cells/metabolism; Female; Humans; Ligands; Mice; Mice, Inbred BALB C; Pneumonia/metabolism; Protein-Serine-Threonine Kinases/metabolism; Receptors, Growth Factor/metabolism; Respiratory Mucosa/cytology; Respiratory Mucosa/metabolism; Respiratory Mucosa/pathology; Signal Transduction/physiology; Smad Proteins; Smad1 Protein; Trans-Activators/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:BMR1B

involved_in

GO:0006954: inflammatory response

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SMAD1

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SMAD5

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:BMP2

involved_in

GO:0006954: inflammatory response

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SMAD1

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:SMAD1

involved_in

GO:0006954: inflammatory response

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:BMP6

involved_in

GO:0006954: inflammatory response

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:SMAD5

part_of

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:ACVR1

involved_in

GO:0002526: acute inflammatory response

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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