Activation of Bone Morphogenetic Protein/Smad Signaling in Bronchial Epithelial Cells during Airway Inflammation

摘要: Bone morphogenetic proteins (BMPs) are pleiotropic secreted proteins, structurally related to transforming growth factor (TGF)- � and activins. BMPs play pivotal roles in the regulation of embryonic lung development branching airways have recently been considered influence inflammatory processes adults due their chemotactic activity on fibroblasts, myocytes, cells. In this study, we investigated possible involvement a model experimental allergic‐airway inflammation situ using antibodies that detect activated Smad monitored modulation BMP ligands during response. Inflamed bronchial epithelial cells few scattered alveolar expressed levels phosphorylated Smad1 (pSmad1/5), indicative active BMP/Smad signaling. This was contrast healthy epithelium, which devoid immunoreactivity. A mechanistic explanation for increased pSmad1/5 staining provided by upregulated expression all type I receptors, i.e., activin receptor‐like kinase (ALK)2, ALK3, ALK6, inflamed Furthermore, mRNA protein profiles were significantly altered airway with induction BMP2, BMP4, BMP6, downregulation BMP5 BMP7. Collectively, our data demonstrate first time BMP/ signaling thus raise possibility could determining role respiratory pathophysiology. Members family central controlling cellular proliferation, differentiation, migration, survival (1). These cytokines constitute highly conserved set whose analogs present organisms from Caenorhabditis elegans mammals indicating essential maintenance tissue homeostasis. The TGF- can be divided into three subgroups: s, activins/inhibins, bone (BMPs), latter constitutes largest subfamily. 30‐35 kD hetero- or homodimeric originally identified ability