3-((4-(6-methylpyridin-2-yl)-5-(quinolin-6-yl)-1h-imidazol-2-yl)methyl)benzamide has been researched along with Pulmonary-Fibrosis* in 1 studies
1 other study(ies) available for 3-((4-(6-methylpyridin-2-yl)-5-(quinolin-6-yl)-1h-imidazol-2-yl)methyl)benzamide and Pulmonary-Fibrosis
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Increased transforming growth factor beta 1 expression mediates ozone-induced airway fibrosis in mice.
Ozone (O₃), a commonly encountered environmental pollutant, has been shown to induce pulmonary fibrosis in different animal models; the underlying mechanism, however, remains elusive. To investigate the molecular mechanism underlying O₃-induced pulmonary fibrosis, 6- to 8-week-old C57BL/6 male mice were exposed to a cyclic O₃ exposure protocol consisting of 2 days of filtered air and 5 days of O₃ exposure (0.5 ppm, 8 h/day) for 5 and 10 cycles with or without intraperitoneal injection of IN-1233, a specific inhibitor of the type 1 receptor of transforming growth factor beta (TGF-β), the most potent profibrogenic cytokine. The results showed that O₃ exposure for 5 or 10 cycles increased the TGF-β protein level in the epithelial lining fluid (ELF), associated with an increase in the expression of plasminogen activator inhibitor 1 (PAI-1), a TGF-β-responsive gene that plays a critical role in the development of fibrosis under various pathological conditions. Cyclic O₃ exposure also increased the deposition of collagens and alpha smooth muscle actin (α-SMA) in airway walls. However, these fibrotic changes were not overt until after 10 cycles of O₃ exposure. Importantly, blockage of the TGF-β signaling pathway with IN-1233 suppressed O₃-induced Smad2/3 phosphorylation, PAI-1 expression, as well as collagens and α-SMA deposition in the lung. Our data demonstrate for the first time that O₃ exposure increases TGF-β expression and activates TGF-β signaling pathways, which mediates O₃-induced lung fibrotic responses in vivo. Topics: Actins; Animals; Benzamides; Bronchi; Collagen; Disease Models, Animal; Inhalation Exposure; Male; Mice; Mice, Inbred C57BL; Oxidants, Photochemical; Ozone; Phosphorylation; Pulmonary Fibrosis; Quinolines; Serpin E2; Signal Transduction; Smad2 Protein; Smad3 Protein; Transforming Growth Factor beta1 | 2011 |