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A7552 - Participation of FIZZ1 in Mouse Model of Silicosis
Author Block: V. Martins1, A. L. da Silva2, P. R. Rocco2, V. Capelozzi1; 1Pathology, University of Sao Paulo Medical School, Sao Paulo, Brazil, 2Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Introduction: Silica is a naturally occurring mineral oxide dust that exists as a crystal structure of silicon dioxide. Inhalation of silica particles causes silicosis: an occupational disease characterized by granuloma formation and accumulation of inflammatory cells that leads to tissue remodeling and impairment of lung function. The pathogenesis of silicosis has been related to the accumulation of inflammatory cells that produce fibrogenic and inflammatory cytokines and growth factors. Although silicosis has been studied intensely, little is known about the crucial cellular mechanisms that initiate and drive the process of inflammation and fibrogenesis. Fibrosis is attributable to excessive synthesis and deposition of collagen and other extracellular matrix (ECM) molecules, accompanied by accumulation of myofibroblast. Myofibroblasts are characterized by expression of α-smooth muscle actin (α-SMA), high contractibility, and production of ECM in response to mechanical strain and soluble stimuli such as transforming growth factor (TGF)-β1 or Found in Inflammatory Zone (FIZZ1). Since FIZZ1 has direct action on myofibroblasts and is involved in the fibrotic process, it is intended, study the role of this molecule and their signaling pathway in fibrogenic mechanisms of silicosis.Methods: Fifteen male mice C57Bl/6, aged 4 to 6 weeks-old with 20-25g, was divided into two groups. The control group (CTRL, n=6), received 50 µl of sterile saline by intratracheal (i.t.) route. The silica group (SIL, n=9), received 20 mg of silica crystals suspended in saline solution (50 µl) by i.t. route. For analysis, all groups were sacrificed on day 14 after induction of Silicosis. The lungs were removed for histology, immunohistochemistry and morphometric analysis. All the experimental procedures were performed according to the guidelines of the internal ethical commission of animals of the University of São Paulo Medical School, Brazil.Results: We found a significant increase of FIZZ1 in SIL group (12.19± 1.65) compared with CTRL group (1.94±0.540). Equally significant was the increased expression of Notch-1 in SIL group (8.43±1.65) compared with CTRL group (0.22±0.13). In addition, SIL group showed significant increase of α-SMA (25.99±2.80) and CD163 (15.23±2.16) when compared with CTRL group (8.88±3.10; 6.37±2.98, respectively).Conclusions: Instillation of silica in mice results in pathological changes that mimic the pattern of human silicosis. Our preliminary data show, for the first time, the participation of FIZZ1 signaling pathway in Silicosis model. Also, we found a M2 macrophage response in SIL group. Indeed, more studies are necessary to elicited the mechanisms that drive the silicosis process.Support: FAPESP, CNPq