Lung Remodeling in a Mouse Model of Asthma Involves a Balance between TGF-beta 1 and BMP-7

• Autor(a) principal: Stumm, Camila Leindecker
• Data de Publicação: 2014
• Outros Autores: Halcsik, Erik, Landgraf, Richardt Gama [UNIFESP], Câmara, Niels Olsen Saraiva [UNIFESP], Sogayar, Mari Cleide, Jancar, Sonia
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://dx.doi.org/10.1371/journal.pone.0095959; http://repositorio.unifesp.br/handle/11600/37678

A key event in chronic allergic asthma is the TGF-beta-induced activation of fibroblasts into alpha-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: alpha-SMA and type-I collagen by immunohistochemistry; BMP-7 and TGF- beta 1 gene expression by qRT-PCR; type-I collagen and Smads 2 and 3 by immunoblotting; mucus by PSA staining. Type-I collagen around bronchi, a-SMA, mucus secretion, TGF- beta 1 and BMP-7 gene expression were all increased in asthma. the TGF- beta 1/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- beta 1 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- beta 1.