Lung remodeling in a mouse model of asthma involves a balance between TGF-β1 and BMP-7

• Published in: PloS one Vol. 9; no. 4; p. e95959
• Main Authors: Stumm, Camila Leindecker, Halcsik, Erik, Landgraf, Richardt Gama, Camara, Niels Olsen Saraiva, Sogayar, Mari Cleide, Jancar, Sonia
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 29.04.2014; Public Library of Science (PLoS)
• Subjects: Alum; Aluminum sulfate; Animals; Asthma; Asthma - metabolism; Asthma - pathology; Base Sequence; Biochemistry; Biological activity; Biology and Life Sciences; Bone Morphogenetic Protein 7 - metabolism; Bronchi; Bronchoalveolar Lavage Fluid; Bronchus; Case-Control Studies; Cells, Cultured; Collagen; Collagen (type I); Collagen - metabolism; Disease Models, Animal; DNA Primers; Experiments; Fibroblasts; Fibrosis; Gene expression; Growth factors; Hypersensitivity; Immunization; Immunoblotting; Immunohistochemistry; Immunology; Inflammation; Lung - metabolism; Lung - pathology; Lungs; Male; Mice; Mice, Inbred BALB C; Mucus; Ovalbumin; Phosphorylation; Proteins; Rodents; Smad protein; Transforming Growth Factor beta1 - metabolism; Transforming growth factor-b1; Brazil
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0095959

A key event in chronic allergic asthma is the TGF-β-induced activation of fibroblasts into α-SMA-positive myofibroblasts which synthesize type-I collagen. In the present study we investigated the effect of the anti-fibrotic molecule BMP-7 in asthma. Balb/c mice were immunized i.p. with ovalbumin in alum and challenged every 2 days with ovalbumin aerosol (two or six challenges for acute and chronic protocols, respectively). The lung was evaluated for: α-SMA and type-I collagen by immunohistochemistry; BMP-7 and TGF- β1 gene expression by qRT-PCR; type-I collagen and Smads 2 and 3 by immunoblotting; mucus by PSA staining. Type-I collagen around bronchi, α-SMA, mucus secretion, TGF- β1 and BMP-7 gene expression were all increased in asthma. The TGF- β1/BMP-7 ratio was higher in the chronic group and correlated with higher levels of collagen. Fibroblasts isolated from asthmatic and healthy lungs produced type-I collagen upon stimulation with TGF- β1 via phosphorylation of Smad-2, Smad-3. Pre-treatment of the fibroblasts with BMP-7 reduced collagen production and Smads phosphorylation. Intranasal treatment of asthmatic mice with recombinant BMP-7 during the immunization protocol reduced lung inflammation and type I collagen deposition. These results suggest a protective role for BMP-7 in lung allergic inflammation, opposing the pro-fibrotic effects of TGF- β1.