ABSTRACT
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-ß1. Both in vivo and in vitro results showed that ISRIB reversed the expression of senescence-related factors ß-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.
Subject(s)
Ataxia Telangiectasia , Pulmonary Fibrosis , Silicosis , Animals , Mice , Pulmonary Fibrosis/chemically induced , Silicon Dioxide/toxicity , X-Ray Microtomography , Alveolar Epithelial CellsABSTRACT
Cellular senescence has been considered an important driver of many chronic lung diseases. However, the specific mechanism of cellular senescence in silicosis is still unknown. In the present study, silicotic rats and osteoclast stimulatory transmembrane protein (Ocstamp) overexpression of MLE-12 cells were used to explore the mechanism of OC-STAMP in cellular senescence in alveolar epithelial cell type II (AEC2). We found an increasing level of OC-STAMP in AEC2 of silicotic rats. Overexpression of Ocstamp in MLE-12 cells promoted epithelial-mesenchymal transition (EMT), endoplasmic reticulum (ER) stress, and cellular senescence. Myosin heavy chain 9 (MYH9) was a potential interacting protein of OC-STAMP. Knockdown of Ocstamp or Myh9 inhibited cellular senescence in MLE-12 cells transfected with pcmv6-Ocstamp. Treatment with 4-phenylbutyrate (4-PBA) to inhibit ER stress also attenuated cellular senescence in vitro or in vivo. In conclusion, OC-STAMP promotes cellular senescence in AEC2 in silicosis.
Subject(s)
Alveolar Epithelial Cells/metabolism , Cellular Senescence , Gene Expression Regulation , Membrane Proteins/biosynthesis , Silicosis/metabolism , Alveolar Epithelial Cells/pathology , Animals , Cell Line , Disease Models, Animal , Rats , Rats, Wistar , Silicosis/pathologyABSTRACT
Cotton leaf roller Sylepta derogata causes serious damage to cotton at the later growing stages of cotton. A leaf-dip method was used to measure the effects of low-concentration CrylAc toxic protein on the development and population growth of three successive generations of cotton leaf rol-lers in this study. The larval duration of Bt-fed S. derogata was 1.78-2.00 d longer, adult life span 1.44-1.94 d longer, and pupal mass 5.3%-11.8% higher than those of the control, respectively. The egg counts per female in the three generations were 65.1%, 47.3% and 37.6% higher, respectively, than those of the control, and the indexes of population trend were 11.4%, 17.5% and 20.0% greater, respectively. No significant differences were found in the duration of pupa duration, the emergence rate, the sex ratio, or the hatch rate. It was suggested that the population of cotton leaf rollers would steadily increase during the later stage of transgenic Bt cotton growth, therefore, further risk assessments of transgenic cotton and comprehensive management of these pests in cotton fields were needed.
Subject(s)
Bacterial Proteins/toxicity , Endotoxins/toxicity , Hemolysin Proteins/toxicity , Lepidoptera , Plants, Genetically Modified , Animals , Bacillus thuringiensis Toxins , Female , Gossypium , Larva , Plant Leaves , Pupa , ReproductionABSTRACT
The heavy metals pollution is one of the ecological problems which have been paid close attention to Spodoptera exigua Hübner, one of the key pests on vegetables and cotton in the Yangtze River and its southern area in China, has broken out more frequently in recent years. In this study, accumulation of Pb2+ in S. exigua and its excretion were detected when fed with artificial diets with different Pb2+ concentrations (0.3, 1.2, 4.8, 19.2 and 76.8 mg x kg(-1), respectively). Life table was constructed according to the survival and growth of different stages of S. exigua. The effect of lead on three successive generations of beet armyworm was studied using the life table in the laboratory. It was found that the Pb2+ contents were significantly different when S. exigua was reared at different Pb2+ concentrations in the same generation in a significant dose-dependent manner. The concentration of Pb2+ increased with prolonging the stress time at the same time. The Pb2+ concentrations at the three developmental stages of beet armyworm followed the order of larvae > adult > pupa. The beet armyworm could excrete heavy metals by means of faeces, prepupa exuviate and puparium, and the concentrations of Pb2+ in faeces and prepupa exuviate were far higher than in puparium. According to the survival rates of different developmental stages, the female ratios and the egg numbers, the laboratory population life table was constructed. It showed that low doses of Pb2+ promoted the growth of the population, and high doses inhibited the growth, and the index of population trend (I) declined more rapidly with the increase of stress time. The study could provide references for long-term and objective assessment of heavy metal hazard and its effect on the populations of important agricultural pests.
