Table 4.
Differential expression of genes in lung cell models.
| Differentially Expressed Genes (DEGs) |
Cellular Response Pathways |
AgNP Size (nm) |
AgNP Coating |
Cell Line | Ref |
|---|---|---|---|---|---|
| p53 ↓, p21↓, Mdm2↓, caspase-3↓ | Cell damage DNA damage Apoptosis |
20 | PVP | A549 | [41] |
| ATM protein ↑, Heme oxygenase-1↑ |
Cell cycle DNA damage Apoptosis |
10, 20 | PVP | A549 | [42] |
| Bax↑, Casp3↑, Casp9↑, miR-192↑, Bcl-2↓ | Cell cycle Apoptosis |
10.63 |
Artemisia
oliveriana |
A549 MRC-5 |
[52] |
| 685 transcripts upregulated and 718 transcripts downregulated in RNA-seq global mRNA levels Bcl-2↓ |
Cell growth (Senescence) Cell Cycle |
25 | PVP | Normal human lung fibroblast (NHLF) MRC-5 |
[130] |
| p53↑, p21↑, Bid↑, Bax↑, Bak ↑, Cyt C↑, Bcl-2↓, Bcl-xL↓ | Enriched signaling pathways; MAPK2, TNF, IL17, P13k-AKT, NF- Kappa B, Apoptosis | 5, 40 | Wogonin | A549 | [113] |
| 719 genes were down-regulated, and 998 genes were up-regulated. Collagen related (COL1A1, COL1A2, COL6A2, COL11A1, COL16A1, COL18A1, COL21A1) ↑ COL17A1 ↓, MMP2 matrix-metallopeptidase involved in the degradation of collagen (IV, V, VII, X) ↑ MMP11, and MMP19 inhibition of metalloproteases ↑ TGFβ1, an important pro-fibrotic growth factor and a key regulator of lung fibrosis and its receptor TGFBR1 ↑, BAMBI ↓, AGTR1, PGF, and PDGF ↑, CDH1 ↑, CDH 12 ↓, NOTCH3 ↑, MMP2 ↑, MRas ↑, HIF1α ↓, Antioxidant enzymes such as glutathione-S-transferases (GSTM1, GSTM2, GSTM3, GSTT2/GSTT2B) ↑, M NQO1 ↑, EPHX1 ↑, CAT ↓ |
Enriched pathways related to: Carcinogenesis, Hepatic fibrosis, ROS, regulation of epithelial mesenchymal transition. |
10, 75 | Citrate | BEAS-2B | [14] |
| TFEB↓, LC3B-II↑, LAMP1→, P62↑, C, Bax↑, Bcl-xL↓, C, Casp3→, NF-kB↓, p53→ | Apoptosis Necrosis |
10, 20 | PVP | 3D and 2D A549 model with and without hydra protein |
[27] |
| 493 differentially regulated transcripts SLC26A4↑, Duox1↑, Ect2↑, sftpa1↑, sftpd↑, muc1↑, cftr↑, MTA1 and MTA2 ↑, NOXO1 and SOD2↑, mir146, mir155, mir21 and mir 224↑ |
Nrf2 Regulation of inflammatory processes Regulation of metals DNA damage cell cycle regulation Inflammatory process Immunomodulatory response ROS Tissue remodeling Metal overload. |
14 | Uncoated | Organotypic-reconstituted 3D human primary small airway epithelial cell |
[59] |
| HMOX-1↑, NQO1↓, SOD1↑ MT-1A, MT-1B and MT-2A↑, Casp7 ↑, FAS↑, HSP70↑, GST↓, VCAM1↑, ICAM-1↓, NF-kB↓, IL-6↑, COX-2↓, N |
Nrf2 regulates inflammatory processes Metal binding antioxidant metallothionein Apoptosis |
20, 200 | Uncoated | 3D model representative of the alveolar barrier |
[60] |
| Drp1↑, p-Drp1↑, Opa1↓, Mfn2↓, Casp3↑ | Fission Fusion Apoptotic |
10–20 | Uncoated | Sprague Dawley Rats | [138] |
p53: cellular division and cellular destruction (tumor suppression); Cas-3: cell death process (apoptosis, necrosis and inflammation); Bax: anti-apoptotic regulator; BCL2: blocks apoptotic death; MMP2 (matrix metalloprotein ase-2): matrix-metallopeptidase involved in degradation of collagens (IV, V, VII, X); NQO1 (NAD(P)H dehydrogenase [quinone] 1): decodes for inducible multifunctional antioxidant enzymes; SOD1 (Superoxide dismutase 1): protein coding gene; NF-KB1 (nuclear Factor Kappa B subunit 1): DNA transcription and immune cell development; PTGS2/COX2 (prostaglandin-endoperoxide synthase 2): mediator of physiological stresses responses such as infection and inflammation; HMOX1 (heme oxygenase 1): inflammatory process and Fe homeostasis; IL6 (interleukin 6): cellular proliferation and long-term survival; Slc26a4: epithelial expressed/mucin regulation; NOTCH3: blood vessels maintenance; TGFβ1: cell growth, cell proliferation, cell differentiation, and apoptosis; sftpd: lung defense against foreign agents and toxins.