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

Abstract

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.

• Authors: Camila Leindecker Stumm, Erik Halcsik, Richardt Gama Landgraf, Niels Olsen Saraiva Camara, Mari Cleide Sogayar, Sonia Jancar
• Journal: PloS one (PLoS One) Vol. 9 Issue 4 Pg. e95959 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 24781156 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bone Morphogenetic Protein 7
• DNA Primers
• Transforming Growth Factor beta1
• bmp7 protein, mouse
• Collagen

Topics

• Animals
• Asthma (metabolism, pathology)
• Base Sequence
• Bone Morphogenetic Protein 7 (metabolism)
• Bronchoalveolar Lavage Fluid
• Case-Control Studies
• Cells, Cultured
• Collagen (metabolism)
• DNA Primers
• Disease Models, Animal
• Lung (metabolism, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Transforming Growth Factor beta1 (metabolism)