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Occupational and Environmental Lung Diseases: Occupational and Environmental Lung Diseases |

Follistatin-like 1 Aggravates Silica-Induced Mouse Lung Injury and Is a Potential Biomarker of Chronic Fibrotic Lung Diseases FREE TO VIEW

Yinshan Fang; Wen Ning
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Nankai University, Tianjin, China


Copyright 2016, American College of Chest Physicians. All Rights Reserved.


Chest. 2016;149(4_S):A416. doi:10.1016/j.chest.2016.02.432
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SESSION TITLE: Occupational and Environmental Lung Diseases

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM

PURPOSE: Occupational inhalation of dust, such as asbestos or crystalline silica, for prolonged periods in the workplace leads to fibrotic lung diseases worldwide. We have previously showed that FSTL1, a secreted extracellular glycoprotein, is a profibrotic factor that is up-regulated in lungs of patients with IPF and bleomycin-injured mouse model. The role of FSTL1 in the development of other fibrotic lung diseases, such as asbestosis, pneumoconiosis and silicosis, is currently unknown.

METHODS: FSTL1 levels in the serum of patients were measured by enzymelinkedimmunosorbent assay. And for the murine silicosis model, C57BL/6 mice were exposed to 0.2 g/Kg of crystalline silica via oropharyngeal aspiration, and the expression of Fstl1 in lung tissues were analysed by qPCR at 0, 7, 14, 21 days post-silica, respectively. To further investigate the role of Fstl1 in the development of silica-induced lung fibrosis, Fstl1+/- mice were used and their lung injury and fibrogenesis were monitored by hydroxyproline content analysis, H&E and masson's trichrome staining. An anti-FSTL1 neutralizing antibody was given on 8, 11, 14 and 17 days after silica treatment and lung tissues were harvested 21 days after injury for fibrogenesis analysis.

RESULTS: Here, we measured an increased FSTL1 levels in the serum of 19 patients with asbestosis and pneumoconiosis than those in the serum of 20 control individuals. Notably, 87.6% (5/6) patients whose FSTL1 levels were above the average value are asbestotic patients. Exposure of mice to crystalline silica via oropharyngeal aspiration confirmed a marked time-dependent increase of FSTL1 in lung tissue and peripheral blood during fibrogenesis. Haploinsufficiency of Fstl1 was protective from silica-induced lung injury. Fstl1+/- mice displayed an attenuated lung interstitial fibrotic phenotype by 21 days, as indicated by the inhibited myofibroblast activation, lower collagen deposition, and less fibrotic areas in lungs, when compared to their WT littermates. Blockage of FSTL1 with a neutralizing antibody in mice reduced silica-induced fibrosis in vivo.

CONCLUSIONS: Our data suggest that FSTL1 plays an important role in lung fibrosis.

CLINICAL IMPLICATIONS: FSTL1 may serve as a novel therapeutic target or a potential peripheral blood biomarker for treatment of asbestosis/pneumoconiosis/silicosis.

DISCLOSURE: The following authors have nothing to disclose: Yinshan Fang, Wen Ning

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