Among them, we found the principal components of major regulatory clusters, involving inflammatory responses (IFNy, IL6, several members of the interleukin 1 pathway, including ILIA, IL1B, IL1RN, and the TNF pathway members TNF, TNFAIP6, TNFSF15, TNFRSF9), angiogenesis (CXCL10, PTGS2), immune regulation (CD80, CD274, CSF3, IL23R), leukocyte chemotaxis (CCL2, CCL3, CCL4, CCL20, CCL23, CCL3L3, CXCL1, CXCL2, CXCL5, CXCL9), transcriptional regulation (EGR1, GATA6, HEY1), proliferation (CDKN2B, FGFR1), adhesion (ITGB8), extracellular matrix remodeling (ADAMTS4), cell-cell communication (GJB2), cell signaling (EDNRB, IRS1, RIN2), ion transmembrane transport (KCNJ2, CLIC4), and response to oxidative stress (SOD2).
IL23R was upregulated in all tested patients one hour postephrin-B2 stimulation, and eight genes (IL1A, IL1B, CCL2, CDKN2B, TNFAIP6, HEY1, ITGB8, and GJB2) were upregulated in all patients four hours poststimulation.
The connectivity degree of each node was calculated, and the top nine nodes with degrees [greater than or equal to] 5 were COL1A1, MMP1, COL3A1, TNC, SPP1, MMP7, POSTN, ITGB8, and COL6A3.
TRIM2 was predicted as the target of 7 microRNAs, and SIX4 and ITGB8 were predicted as the target of five microRNAs.
There are 8 out of 10 downregulated DEGs that are downregulated in Group II compared with those in Group I, namely VIPR1, SLC6A4, NECAB1, LEPREL1, ITLN2, HSD17B6, HHIP, and CRTAC1 and 14 out of 57 upregulated DEGs that are upregulated in Group II compared with those in Group I, namely TRIM2, TP63, TMPRSS4, SPP1, SIX4, MMP1, ITGB8, GOLM1, CP, COL17A1, CLIC6, CDH3, CD24, and C12orf75.
Specifically, BCL2-antagonist/killer 1 (BAK1; catalog Number QT00228508), caspase 2, apoptosis-related cysteine peptidase (CASP2; QT01342509), integrin, beta 8 (ITGB8; QT00038507), mitogen-activated protein kinase kinase 7 (MAP2K7; QT00090545), myeloid cell leukemia sequence 1 (BCL2-related) (MCL1; QT00094122), and the rapamycin-insensitive companion of mTOR (RICTOR; QT00065793) were evaluated for potential changes in gene expression levels induced by formaldehyde exposure.
Target Full Name Context Pct Score ASH1L ashl (absent, small, or -0.59 > homeotic)-like (Drosophila) 0.99 RICTOR rapamycin-insensitive companion of -0.57 > mTOR 0.99 ITGB8 integrin, beta 8 -0.62 0.98 C20orf194 chromosome 20 open reading frame -0.72 0.97 194 SNF1LK SNF1-like kinase -0.39 0.97 FAM44B family with sequence similarity 44, -0.65 0.95 member B C10orf18 chromosome 10 open reading frame 18 -0.87 0.95 ZCCHC14 zinc finger, CCHC domain containing -0.5 0.94 14 AFF1 AF4/FMR2 family, member 1 -0.25 0.94 EML4 echinoderm microtubule associated -0.42 0.93 protein like 4 LCOR ligand dependent nuclear receptor -0.33 0.93 corepressor CCDC6 coiled-coil domain containing 6 -0.33 0.92 BNC2 basonuclin 2 -0.32 0.9 Apoptosis signaling is associated with miR-125b predicted targets.
Canonical Pathways p-value miR-142-3p Predicted Targets ILK Signaling 0.008 ITGB8, RICTOR Role of IL-17F in Allergic 0.031 SIK1 Inflammatory Airway Diseases Macropinocytosis Signaling 0.048 ITGB8 ILK-related miR-142-3p targets are altered in expression.
To test our prediction that formaldehyde alters ILK signaling, the expression levels of genes involved in ILK signaling were assessed, including ITGB8 and RICTOR.
Among them is miR-145, which regulates corneal epithelium formation and maintenance of epithelial integrity, by targeting the expression of integrin ITGB8
Of all the regulated integrin genes identified, only integrin aV (ITGAV) and ITGB8
were up-regulated in both cell populations (see Supplemental Material, Figure S4).