Table 6 Validation of results from mouse and rat models in humans
| Â | OMIC methods used in rodent and main results | Type of silica exposure in rodents (acute or chronic) and time of outcome assessment (early or long-term outcome assessment) | Validation of omic results in rodent | Comparison of results in patient samples |
|---|---|---|---|---|
Pang et al. [22] | LC–MS data shown higher levels of TXA2, PGD2 and PGE2 synthases in the silicosis mouse lungs compared to control mice | Acute exposure and long-term outcome assessment | Immunohistochemistry, qPCR and western blot allowed to validate the results for TXA2 and PGD2 but not for PGE2 | The AA metabolic pathway was enriched in the lungs of silicosis patients using RNA-seq. The mRNA and protein expression levels of PGD2 and TXA2 synthases were also increased in the lungs of silicosis patients compared with control (qPCR, western blot) |
Shichino et al. [24] | 3' SAGE-seq data has revealed gene modules, one upregulated and the other downregulated during fibrosis development in lung fibroblasts from mice exposed to cSiO2. The expression of the transcription factor Srebf1 was downregulated during the lung fibrosis process | Acute exposure and long-term outcome assessment | ND | The gene set enrichment analysis (GSEA) of public transcriptome data from whole lungs or lung fibroblasts of human IPF patient showed that gene modules upregulated during fibrosis progression in mice were also enriched in human samples. However, gene modules downregulated in silicosis mice were more enriched in the lungs of healthy patients. The mRNA expression of SREBF1 was downregulated in human lung fibroblasts derived from IPF patients |
Gao et al. [40] | miRNA-seq identified downregulation of the miR-411-3p in the lungs of rat exposed to cSiO2 | Chronic exposure and long-term outcome assessment | The miR-411-3p levels was lower in cSiO2-exposed rats lungs compared to control rats by in situ hybridization | The in situ hybridization technique showed lower levels of miR-411-3p in the lungs of silicosis patients |
Ji et al. [42] | miRNA microarray has revealed a downregulation of miR-486-5p in cSiO2-exposed mice lungs | Acute exposure and long-term outcome assessment | The downregulation of miR-486-5p in cSiO2-exposed mice lungs is validated by qPCR | The miR-486-5p is downregulated in the serum from silicosis patients (qPCR). It was also downregulated in the lungs of IPF and silicosis patients (qPCR) |
Cai et al. [20] | mRNA-seq analyses of lungs from rats exposed to cSiO2 shown an upregulation of Spp1 expression, compared to non-exposed rats | Chronic exposure and long-term outcome assessment | Higher levels of Spp1 proteins were shown in the cSiO2-exposed rat lungs by western blot and immunohistochemistry | Spp1 protein levels were significantly higher in the serum from silicosis patients (ELISA) and its expression was associated with lung functions |
Shichino et al. [56] | mRNA Microarray on CD45- cells isolated from cSiO2-exposed mice shown an upregulation of Tnc, Mmp2, Grem1, Loxl2, Mmp14 and Thbs2 gene expression | Acute exposure and long-term outcome assessment | The upregulation of Tnc, Mmp2, Grem1, Loxl2, Mmp14 and Thbs2 expression in CD45- cell from cSiO2-exposed mice was validated by qPCR | The analysis of data from public transcriptome data on IPF patient showed an upregulation of Mmp2, Grem1, Mmp14, Thbs2, Loxl2, Tnc gene expression in lung samples from IPF patient compared to healthy patient, that was similar to mice results |
Koli et al. [45] | mRNA Microarray identified an upregulation of Grem1 gene expression in the lung of cSiO2-exposed mice | Acute exposure and long-term outcome assessment | ND | The Grem1 gene expression was higher in lung tissues and lung fibroblasts isolated from IPF patients (qPCR) |