Gene network analysis for identification of microRNA biomarkers for asthma (1)
miRNAs are small, non-coding RNAs that negatively regulate post-transcriptional gene expression via mRNA destabilization or/and degradation. Recent studies have focused on the potential use of miRNAs as biomarkers in various inflammatory diseases, including asthma.
These mice also showed a substantial elevation in the concentration of serum HDM-specific IgE relative to the saline controls.
Hematoxylin–eosin (H&E) staining revealed that HDM mice had a substantial increase in lung inflammation and thicker airways than the saline controls. However, the collagen deposition levels were unchanged between the two groups.
The secretion of major Th2 cytokines, IL-4, 5, 6, 10, and 13, were significantly enhanced in HDM mice compared to the controls. In contrast, IL-1α levels were reduced in HDM mice relative to controls.
The production levels of chemokines, including eotaxin/ CCL11, IP-10/CXCL10, KC/CXCL3, MCP-1/CCL2, MIG/CXCL9 and MIP-1β/CCL4, and were significantly higher in BAL fluid of HDM mice relative to saline controls.
Principal component analysis (PCA) of miRNA expres- sion in lung samples showed two nicely separated clusters between mice treated with saline and HDM. Further analysis of the lung miRNA profile indicated that 125 miRNAs were up-regulated and 88 miRNAs were downregulated by at least 1.5-fold change in HDM mice compared to saline control.
Interferon gamma (IFNγ), Th2 cytokines (IL-4, IL-5, IL-6, IL-10, and IL-13), monocyte chemoattractant protein-1 (MCP-1/ CCL2), transforming growth factor beta 1 (TGFβ1), and matrix metallopeptidase 9 (MMP9) associated miRNAs can be maker candidates for asthma diagnosis, prognosis, and response of therapy (efficacy and safety).
22 of the 30 miRNAs were associated with total IgE levels, AHR, and inflammation.