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| Author(s): |
Camila Leindecker Stumm
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2012-06-19 |
| Examining board members: |
Sonia Jancar Negro;
Luisa Karla de Paula Arruda;
Vera Luiza Capelozzi;
Itamar Souza de Oliveira Junior;
Maria Notomi Sato
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| Advisor: | Sonia Jancar Negro |
| Abstract | |
Allergic asthma is a chronic inflammatory disease of the airways that involves activation of lung fibroblasts. This activation is induced by TGF-<font face=\"Symbol\">b and this process is regulated by anti-fibrotic molecules. Our goal was to elucidate mechanisms involved in airway fibrosis in an animal model of asthma. In the first part, we investigated the PGE2 synthesis/response axis. PGE2 and its analog forskolin inhibited collagen I synthesis and proliferation of fibroblasts. These cells showed a time-dependent loss in the ability to synthesize PGE2 under IL-1<font face=\"Symbol\">b stimulation, and downregulated COX-2 and mPGEs-1. In the second part, we studied the ratio TGF-<font face=\"Symbol\">b1/BMP-7 in airway fibrosis. There is predominance of the pro-fibrotic TGF-<font face=\"Symbol\">b1 over the anti-fibrotic BMP-7 in the lungs of asthmatic animals. In fibroblasts, BMP-7 inhibits TGF-<font face=\"Symbol\">b1-induced type I collagen synthesis and the SMAD-2, SMAD-3 and p38 pathways. Treatment of the animals with BMP-7 caused significant decrease in fibrosis. The results implicate these mechanisms in airway fibrosis in asthma. (AU) | |