Journal
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
Volume 264, Issue -, Pages -Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ecoenv.2023.115410
Keywords
AEC2; Fibrosis; ISRIB; Senescence; Silicosis
Categories
Ask authors/readers for more resources
The effects of integrated stress response inhibitor (ISRIB) on cellular senescence and pulmonary fibrosis in silicosis were evaluated. ISRIB significantly reduced the degree of pulmonary fibrosis and reversed the expression of senescence-related factors in mice with silicosis. These findings suggest that ISRIB may alleviate pulmonary fibrosis in silicosis by inhibiting cellular senescence.
The role and mechanisms of integrated stress response inhibitor (ISRIB) on silicosis are still not well defined. In the present study, the effects of ISRIB on cellular senescence and pulmonary fibrosis in silicosis were evaluated by RNA sequencing, micro-computed tomography, pulmonary function assessment, histological examination, and Western blot analysis. The results showed that ISRIB significantly reduced the degree of pulmonary fibrosis in mice with silicosis and reduced the expression of type I collagen, fibronectin, & alpha;-smooth muscle actin, and transforming growth factor-& beta;1. Both in vivo and in vitro results showed that ISRIB reversed the expression of senescence-related factors & beta;-galactosidase, phosphor-ataxia telangiectasia mutated, phosphor-ataxia telangiectasia and Rad3-related protein, p-p53, p21, p16, and plasminogen activator inhibitor type 1. The aforementioned results were consistent with the sequencing results. These findings implied that ISRIB might reduce the degree of pulmonary fibrosis in mice with silicosis by inhibiting the cellular senescence of alveolar epithelial cell type II.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available