Analysis of the role of long non-coding RNAs involved in silica-induced pulmonary fibrosis of rat
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PROVIDER: PRJNA479818 | ENA |
REPOSITORIES: ENA
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Project description:Mounting evidence suggests that long non-coding RNAs (lncRNAs) are involved in the pathogenesis of silicosis. In this study, Wistar rats were treated with an improved intubation method to ferry silicon dioxide (1mL per rat) into lung. Rats in the control group were injected with normal saline solution (1mL per rat). Twenty eight days after exposure, we examined the rats and found the formation of lung fibrosis in rats treated with silica. We then investigated the lncRNAs expression changes in lungs of silica-exposed rats and compared with that of rats in the control group. Treatment of silica leads to 682 lncRNAs differentially expressed including 300 upregulated and 382 down regulated compared to controls.
2021-07-03 | GSE116653 | GEO
Project description:The pathophysiology of silicosis is poorly understood, limiting development of therapies for those who have been exposed to the respirable particle. We explored mechanisms of silica-induced pulmonary fibrosis in human lung samples collected from patients with occupational exposure to silica and in a longitudinal mouse model of silicosis using multiple modalities including whole-lung single-cell RNA sequencing and histological, biochemical, and physiologic assessments. In addition to pulmonary inflammation and fibrosis, intratracheal silica challenge induced osteoclast-like differentiation of alveolar macrophages and recruited monocytes, driven by induction of the osteoclastogenic cytokine, receptor activator of nuclear factor κΒ ligand (RANKL) in pulmonary lymphocytes, and alveolar type II cells. Anti-RANKL monoclonal antibody treatment suppressed silica-induced osteoclast-like differentiation in the lung and attenuated pulmonary fibrosis. We conclude that silica induces differentiation of pulmonary osteoclast-like cells leading to progressive lung injury, likely due to sustained elaboration of bone-resorbing proteases and hydrochloric acid. Interrupting osteoclast-like differentiation may therefore constitute a promising avenue for moderating lung damage in silicosis.
2024-08-12 | GSE274372 | GEO
Project description:microRNAs (miRNAs) play a critical biological role in a variety of pathophysiological processes by suppressing their target genes. However, little is known on the miRNAs expression profiles of lung tissues in silica-induced pulmonary fibrosis. To investigate miRNAs of interest in regulation of pulmonary fibrosis, total RNA was isolated from mice lungs collected at day 0, day 3, day 7, day 14, day 28 and day 56 after silica exposure. Then, miRNA microarray was performed with one mouse lung at each time point. miRNA microarray was performed with one mouse lung at day 0, day 3, day 7, day 14, day 28 and day 56 after silica exposure to investigate the miRNAs expression profiles of lung tissues in silica-induced pulmonary fibrosis. Mouse lung tissues were selected at each time point after treatment for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain homogeneous populations of lungs at each fibrotic stage in order to increase the temporal resolution of expression profiles. To that end, we hand-selected lung tissues according to morphological criteria at five time-points: before silica exposure, i.e. day 0 (D0), the early inflammation phase day 3 (D3) and day 7 (D7), the late inflammation phase, day 14 (D14), the fibrosis phase,i.e. day 28 (D28) and day (D56).
2014-01-29 | E-GEOD-54463 | biostudies-arrayexpress
Project description:microRNAs (miRNAs) play a critical biological role in a variety of pathophysiological processes by suppressing their target genes. However, little is known on the miRNAs expression profiles of lung tissues in silica-induced pulmonary fibrosis. To investigate miRNAs of interest in regulation of pulmonary fibrosis, total RNA was isolated from mice lungs collected at day 0, day 3, day 7, day 14, day 28 and day 56 after silica exposure. Then, miRNA microarray was performed with one mouse lung at each time point. miRNA microarray was performed with one mouse lung at day 0, day 3, day 7, day 14, day 28 and day 56 after silica exposure to investigate the miRNAs expression profiles of lung tissues in silica-induced pulmonary fibrosis.
2014-01-29 | GSE54463 | GEO
Project description:Pulmonary osteoclast-like cells in silica induced pulmonary fibrosis
| PRJNA1146078 | ENA
Project description:Pulmonary fibrosis (PF) is an intractable disorder with a poor prognosis. Although lung fibroblasts play central roles in PF, their key regulatory molecules remain unclear. To identify PF pathology-associated gene modules and their hub TFs in activated lung fibroblasts, we performed time-course transcriptome analysis of the fibroblasts purified from the lungs of bleomycin- and silica-treated Col1a2-GFP reporter mice.
2019-01-30 | GSE110540 | GEO
Project description:A proper understanding of the mechanisms underlying crystalline silica-induced pulmonary toxicity has implications in the management and potential prevention of the adverse health effects associated with silica exposure including silicosis, cancer and several auto-immune diseases. Human lung type II epithelial cells and rat lungs exposed to crystalline silica were employed as experimental models to determine global gene expression changes in order to understand the molecular mechanisms underlying silica-induced pulmonary toxicity. The differential gene expression profile induced by silica correlated with its toxicity in the A549 cells. The biological processes perturbed by silica exposure in the A549 cells and rat lungs, as identified by the bioinformatic analysis of the differentially expressed genes, demonstrated significant similarity. Functional categorization of the differentially expressed genes identified cancer, cellular movement, cellular growth and proliferation, cell death, inflammatory response, cell cycle, cellular development, and genetic disorder as top-ranking biological functions perturbed by silica exposure in the A549 cells and rat lungs. The involvement of oxidative stress and apoptosis in the silica-induced pulmonary toxicity was confirmed by ELISA and confocal microscopy analysis, respectively, of the silica-exposed A549 cells. Results of our study, in addition to confirming several previously identified molecular targets and mechanisms involved in silica toxicity, identified novel molecular targets and mechanisms potentially involved in silica-induced pulmonary toxicity. Further investigations, including those focused on the novel molecular targets and mechanisms identified in the current study, may result in a better management and, possibly, reduction and/or prevention of the potential adverse health effects associated with crystalline silica exposure.
2012-06-30 | GSE30178 | GEO
Project description:The capability to detect target organ toxicity as well as to determine the molecular mechanisms underlying such toxicity by employing surrogate biospecimens that can be obtained by a non-invasive or minimally invasive procedure has significant advantage in occupational toxicology. Pulmonary toxicity and global gene expression profile in the lungs, peripheral blood and bronchoalveolar lavage (BAL) cells were determined in rats at 44-weeks following pulmonary exposure to crystalline silica (15 mg/m3, 6-hours/day, 5 days). A significant elevation in lactate dehydrogenase activity and albumin content observed in the BAL fluid suggested the induction of pulmonary toxicity in the silica exposed rats. Similarly, the observation of histological alterations, mainly type II pneumocyte hyperplasia and fibrosis, in the lungs further confirmed silica-induced pulmonary toxicity in the rats. A significant increase in the number of neutrophils and elevated monocyte chemotactic protein 1 level in the BAL fluids suggested silica-induced pulmonary inflammation in the rats. Determination of global gene expression profile in the lungs, BAL cells, and peripheral blood of the silica exposed rats identified 144, 236, and 51 significantly differentially expressed genes (SDEGs), respectively, compared with the corresponding control samples. Bioinformatics analysis of the SDEGs demonstrated a remarkable similarity in the biological functions, molecular networks and canonical pathways that were significantly affected by silica exposure in the lungs, BAL cells and blood of the rats. Induction of inflammation was identified, based on the bioinformatics analysis of the significantly differentially expressed genes in the lungs, blood and BAL cells, as the major molecular mechanism underlying the silica-induced pulmonary toxicity. The findings of our study demonstrated the potential application of global gene expression profiling of peripheral blood and BAL cells as a valuable minimally invasive approach to study silica-induced pulmonary toxicity in rats.
2017-06-20 | GSE41572 | GEO
Project description:Identification of molecular target(s) and mechanism(s) of silica-induced pulmonary toxicity is important for the intervention and/or prevention of diseases associated with occupational exposure to crystalline silica. Rats were exposed to crystalline silica by inhalation (15 mg/m3, 6 h/day, 5 days) and global gene expression profile was determined in the lungs by microarray analysis at 1, 2, 4, 8, and 16 weeks following termination of silica exposure. The number of significantly differentially expressed genes (>1.5 fold change and <0.01 FDR p value) detected in the lungs during the post-exposure time intervals analyzed exhibited a steady increase in parallel with the progression of silica-induced pulmonary toxicity noticed in the rats. Quantitative real-time PCR analysis of a representative set of 10 genes confirmed the microarray findings. The various biological functions, canonical pathways, and molecular networks affected by silica exposure, as identified by the bioinformatics analysis of the significantly differentially expressed genes, also exhibited a steady increase similar to the silica-induced pulmonary toxicity. Genes involved in oxidative stress, inflammation, respiratory diseases, cancer, and tissue remodeling and fibrosis were significantly differentially expressed in the rat lungs; however, unresolved lung inflammation was the single most significant biological response to pulmonary exposure to crystalline silica. Excessive mucus production, as implicated by significant overexpression of the pendrin coding gene, SLC26A4, was identified as a novel mechanism for silica-induced pulmonary toxicity. Collectively, the findings of our study provided insights into the molecular mechanisms underlying the progression of crystalline silica-induced pulmonary toxicity in the rat and these findings may be useful in future to develop strategies to prevent occupational silicosis. A total of 60 rat lung samples were analyzed in this gene expression experiment. Rats were exposed to crystalline silica at a concentration of 15 mg/m³, 6-hours/day for 5 consecutive days. Rats exposed simultaneously to filtered air served as the controls. The control (n=4) and silica exposed (n=8) rats were sacrificed at post-exposure time intervals of 1, 2, 4, 8, and 16 weeks following termination of silica exposure and lung gene expression profile was determined.
2012-06-29 | E-GEOD-32147 | biostudies-arrayexpress
Project description:Identification of molecular target(s) and mechanism(s) of silica-induced pulmonary toxicity is important for the intervention and/or prevention of diseases associated with occupational exposure to crystalline silica. Rats were exposed to crystalline silica by inhalation (15 mg/m3, 6 h/day, 5 days) and global gene expression profile was determined in the lungs by microarray analysis at 1, 2, 4, 8, and 16 weeks following termination of silica exposure. The number of significantly differentially expressed genes (>1.5 fold change and <0.01 FDR p value) detected in the lungs during the post-exposure time intervals analyzed exhibited a steady increase in parallel with the progression of silica-induced pulmonary toxicity noticed in the rats. Quantitative real-time PCR analysis of a representative set of 10 genes confirmed the microarray findings. The various biological functions, canonical pathways, and molecular networks affected by silica exposure, as identified by the bioinformatics analysis of the significantly differentially expressed genes, also exhibited a steady increase similar to the silica-induced pulmonary toxicity. Genes involved in oxidative stress, inflammation, respiratory diseases, cancer, and tissue remodeling and fibrosis were significantly differentially expressed in the rat lungs; however, unresolved lung inflammation was the single most significant biological response to pulmonary exposure to crystalline silica. Excessive mucus production, as implicated by significant overexpression of the pendrin coding gene, SLC26A4, was identified as a novel mechanism for silica-induced pulmonary toxicity. Collectively, the findings of our study provided insights into the molecular mechanisms underlying the progression of crystalline silica-induced pulmonary toxicity in the rat and these findings may be useful in future to develop strategies to prevent occupational silicosis.
2012-06-30 | GSE32147 | GEO