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PLoS One. 2014 Apr 29;9(4):e95959. doi: 10.1371/journal.pone.0095959. eCollection 2014.

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

Author information

1
Department of Immunology, University of Sao Paulo, Sao Paulo, SP, Brazil.
2
Department of Biochemistry, University of Sao Paulo, Sao Paulo, SP, Brazil.
3
Department of Biological Sciences, Federal University of Sao Paulo, Diadema, SP, Brazil.
4
Department of Immunology, University of Sao Paulo, Sao Paulo, SP, Brazil; Division of Nephrology, Federal University of Sao Paulo, Sao Paulo, SP, Brazil.

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.

PMID:
24781156
PMCID:
PMC4004563
DOI:
10.1371/journal.pone.0095959
[Indexed for MEDLINE]
Free PMC Article

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