Lung remodeling in a mouse model of asthma involves a balance between TGF-β1 and BMP-7.
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4004563?pdf=render |
| _version_ | 1818321443530735616 |
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| author | Camila Leindecker Stumm Erik Halcsik Richardt Gama Landgraf Niels Olsen Saraiva Camara Mari Cleide Sogayar Sonia Jancar |
| author_facet | Camila Leindecker Stumm Erik Halcsik Richardt Gama Landgraf Niels Olsen Saraiva Camara Mari Cleide Sogayar Sonia Jancar |
| author_sort | Camila Leindecker Stumm |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T10:40:59Z |
| format | Article |
| id | doaj.art-2a6decab746a45e1a3c1f4850016bb22 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T10:40:59Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-2a6decab746a45e1a3c1f4850016bb222022-12-21T23:50:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9595910.1371/journal.pone.0095959Lung remodeling in a mouse model of asthma involves a balance between TGF-β1 and BMP-7.Camila Leindecker StummErik HalcsikRichardt Gama LandgrafNiels Olsen Saraiva CamaraMari Cleide SogayarSonia JancarA 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.http://europepmc.org/articles/PMC4004563?pdf=render |
| spellingShingle | Camila Leindecker Stumm Erik Halcsik Richardt Gama Landgraf Niels Olsen Saraiva Camara Mari Cleide Sogayar Sonia Jancar Lung remodeling in a mouse model of asthma involves a balance between TGF-β1 and BMP-7. PLoS ONE |
| title | Lung remodeling in a mouse model of asthma involves a balance between TGF-β1 and BMP-7. |
| title_full | Lung remodeling in a mouse model of asthma involves a balance between TGF-β1 and BMP-7. |
| title_fullStr | Lung remodeling in a mouse model of asthma involves a balance between TGF-β1 and BMP-7. |
| title_full_unstemmed | Lung remodeling in a mouse model of asthma involves a balance between TGF-β1 and BMP-7. |
| title_short | Lung remodeling in a mouse model of asthma involves a balance between TGF-β1 and BMP-7. |
| title_sort | lung remodeling in a mouse model of asthma involves a balance between tgf β1 and bmp 7 |
| url | http://europepmc.org/articles/PMC4004563?pdf=render |
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