title: Altered Expression of Bone Morphogenetic Protein Accessory Proteins in Murine and Human Pulmonary Fibrosis.
abstract: Idiopathic pulmonary fibrosis is a chronic, progressive fibrotic disease with a poor prognosis. The balance between transforming growth factor β1 and bone morphogenetic protein (BMP) signaling plays an important role in tissue homeostasis, and alterations can result in pulmonary fibrosis. We hypothesized that multiple BMP accessory proteins may be responsible for maintaining this balance in the lung. Using the bleomycin mouse model for fibrosis, we examined an array of BMP accessory proteins for changes in mRNA expression. We report significant increases in mRNA expression of gremlin 1, noggin, follistatin, and follistatin-like 1 (Fstl1), and significant decreases in mRNA expression of chordin, kielin/chordin-like protein, nephroblastoma overexpressed gene, and BMP and activin membrane-bound inhibitor (BAMBI). Protein expression studies demonstrated increased levels of noggin, BAMBI, and FSTL1 in the lungs of bleomycin-treated mice and in the lungs of idiopathic pulmonary fibrosis patients. Furthermore, we demonstrated that transforming growth factor β stimulation resulted in increased expression of noggin, BAMBI, and FSTL1 in human small airway epithelial cells. These results provide the first evidence that multiple BMP accessory proteins are altered in fibrosis and may play a role in promoting fibrotic injury.
authors.affiliation: School of Medicine, Conway Institute, University College Dublin, Dublin, Ireland; Department of Anaesthesia and Intensive Care Medicine, St Vincent's University Hospital, Dublin, Ireland.
authors.forename: Noelle
authors.initials: N
authors.lastname: Murphy
authors.affiliation: School of Medicine, Conway Institute, University College Dublin, Dublin, Ireland.
authors.forename: Katherine U
authors.initials: KU
authors.lastname: Gaynor
authors.affiliation: School of Medicine, Conway Institute, University College Dublin, Dublin, Ireland.
authors.forename: Simon C
authors.initials: SC
authors.lastname: Rowan
authors.affiliation: School of Medicine, Conway Institute, University College Dublin, Dublin, Ireland; School of Medicine, St Vincent's University Hospital, Dublin, Ireland.
authors.forename: Sinead M
authors.initials: SM
authors.lastname: Walsh
authors.affiliation: Department of Histopathology, St Vincent's University Hospital, Dublin, Ireland.
authors.forename: Aurelie
authors.initials: A
authors.lastname: Fabre
authors.affiliation: Department of Anaesthesia and Intensive Care Medicine, St Vincent's University Hospital, Dublin, Ireland.
authors.forename: John
authors.initials: J
authors.lastname: Boylan
authors.affiliation: School of Medicine, Conway Institute, University College Dublin, Dublin, Ireland; School of Medicine, St Vincent's University Hospital, Dublin, Ireland.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Keane
authors.affiliation: School of Medicine, Conway Institute, University College Dublin, Dublin, Ireland; School of Medicine, St Vincent's University Hospital, Dublin, Ireland. Electronic address: paul.mcloughlin@ucd.ie.
authors.forename: Paul
authors.initials: P
authors.lastname: McLoughlin
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D001761:Bleomycin / Q000009:adverse effects; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism; D038702:Follistatin-Related Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D008168:Lung / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D015398:Signal Transduction; D013047:Specific Pathogen-Free Organisms; D053773:Transforming Growth Factor beta1 / Q000235:genetics* / Q000378:metabolism; D000099176:Noggin Protein
chemical_list: D001761:Bleomycin; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D038702:Follistatin-Related Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D000099176:Noggin Protein; C485671:BAMBI protein, human; C448799:FSTL1 protein, human