Genetic loss of Gas6/Mer pathway attenuates silica-induced lung inflammation and fibrosis in mice

•Gas6 level in BALF elevated persistently from day 7 to 84 in silica-treated mice.•Gas6 or Mer deficiency limited the silica-induced pulmonary inflammation.•Gas6 or Mer deficient mice exhibited an alleviated pulmonary fibrosis. Long-term inhalation of crystalline silica particles leads to silicosis...

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Bibliographic Details
Published in:Toxicology letters 2019-10, Vol.313, p.178-187
Main Authors: Li, Wei, Xie, Li, Ma, Jixuan, Yang, Meng, Wang, Bin, Xu, Yiju, Fan, Lieyang, Mu, Ge, Shi, Tingming, Chen, Weihong
Format: Article
Language:English
Subjects:
Gas6
Lung fibrosis
Lung inflammation
Mer
Silica particles
Silicosis
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Summary:•Gas6 level in BALF elevated persistently from day 7 to 84 in silica-treated mice.•Gas6 or Mer deficiency limited the silica-induced pulmonary inflammation.•Gas6 or Mer deficient mice exhibited an alleviated pulmonary fibrosis. Long-term inhalation of crystalline silica particles leads to silicosis characterized by pulmonary inflammation and interstitial fibrosis. The growth arrest-specific protein 6 (Gas6) and its tyrosine receptor Mer have been implicated to involve in the regulation of inflammation, innate immunity and tissue repair. However, the role of Gas6 or Mer in silica-induced lung inflammation and fibrosis has not been investigated previously. In this study, we observed a remarkable increase of Gas6 in bronchoalveolar lavage fluid (BALF) from wild-type C57BL/6 mice after silica intratracheal administration. Then, we investigated whether genetic loss of Gas6 or Mer could attenuate silica-induced lung inflammation and fibrosis. Our results showed that Gas6−/− and Mer−/− mice exhibited reduced lung inflammation response from days 7 to 84 after silica exposure. We also uncovered an overexpression of the suppressor of cytokine signaling protein 1 in silica-treated deficient mice. Moreover, Gas6 or Mer deficiency attenuated silica-induced collagen deposition by inhibiting the expression of transforming growth factor-β. We conclude that gene absence of Gas6 or Mer is protective against silica-induced lung inflammation and fibrosis in mice. Targeting Gas6/Mer pathway may be a potential therapeutic approach to treat pulmonary fibrosis in patients with silicosis.
ISSN:0378-4274
1879-3169
DOI:10.1016/j.toxlet.2019.07.008