School of public and health, Hebei Key Laboratory for Organ Fibrosis Research, North China University of Science and Technology, Tangshan, China.
School of public and health, Hebei Key Laboratory for Organ Fibrosis Research, North China University of Science and Technology, Tangshan, China; NHC Key Laboratory of Pneumoconiosis，Department of Pulmonary and Critical Care Medicine, The First Hospital of Shanxi Medical University, Taiyuan, China.
Ecotoxicol Environ Saf. 2023 Oct 1;264:115410. doi: 10.1016/j.ecoenv.2023.115410. Epub 2023 Aug 28.
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, α-smooth muscle actin, and transforming growth factor-β1. Both in vivo and in vitro results showed that ISRIB reversed the expression of senescence-related factors β-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.
整合应激反应抑制剂（ISRIB）在矽肺中的作用和机制尚不清楚。本研究通过 RNA 测序、微计算机断层扫描、肺功能评估、组织学检查和 Western blot 分析，评估了 ISRIB 对矽肺细胞衰老和肺纤维化的影响。结果表明，ISRIB 可显著降低矽肺小鼠的肺纤维化程度，降低Ⅰ型胶原、纤连蛋白、α-平滑肌肌动蛋白和转化生长因子-β1 的表达。体内和体外结果均表明，ISRIB 逆转了衰老相关因子β-半乳糖苷酶、共济失调毛细血管扩张突变相关蛋白、共济失调毛细血管扩张和 Rad3 相关蛋白、p53、p21、p16 和纤溶酶原激活物抑制剂 1 的表达。上述结果与测序结果一致。这些发现表明，ISRIB 可能通过抑制肺泡上皮细胞Ⅱ型的细胞衰老来降低矽肺小鼠的肺纤维化程度。
