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

Abstract

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.

• Authors: Wei Li, Li Xie, Jixuan Ma, Meng Yang, Bin Wang, Yiju Xu, Lieyang Fan, Ge Mu, Tingming Shi, Weihong Chen
• Journal: Toxicology letters (Toxicol Lett) Vol. 313 Pg. 178-187 (Oct 01 2019) ISSN: 1879-3169 [Electronic] Netherlands
• PMID: 31284023 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Collagen Type I
• Intercellular Signaling Peptides and Proteins
• Socs1 protein, mouse
• Suppressor of Cytokine Signaling 1 Protein
• Transforming Growth Factor beta
• growth arrest-specific protein 6
• Mertk protein, mouse
• c-Mer Tyrosine Kinase

Topics

• Animals
• Collagen Type I (genetics, metabolism)
• Disease Models, Animal
• Intercellular Signaling Peptides and Proteins (deficiency, genetics)
• Lung (enzymology, pathology)
• Male
• Mice, Inbred C57BL
• Mice, Knockout
• Pneumonia (enzymology, genetics, pathology, prevention & control)
• Pulmonary Fibrosis (enzymology, genetics, pathology, prevention & control)
• Signal Transduction
• Silicosis (enzymology, genetics, pathology, prevention & control)
• Suppressor of Cytokine Signaling 1 Protein (genetics, metabolism)
• Time Factors
• Transforming Growth Factor beta (genetics, metabolism)
• c-Mer Tyrosine Kinase (deficiency, genetics)