Table 1.
Involvement of EGR1 in COPD (see text for more detail)
| Disease or Model of Disease | Interactions/Mechanism | References |
|---|---|---|
| Cigarette smoke induces human bronchial epithelium (16-HBE) | Cigarette smoke extract induces PIGF release from human bronchial epithelial cells via the ROS/MAPK (ERK-1/2)/EGR1 axis; EGR1 binds to the PIGF promoter, promoting high PlGF expression to further mediate apoptosis and exacerbate emphysema. | Wu et al. (97) |
| Cigarette smoke stimulates C57BL/6 mice and BEAS-2B cells | GGPPS is a target gene of EGR1 and MAPK ERK/EGR1/GGPPS/MAPK form a positive feedback loop that exacerbates cigarette smoke-induced lung inflammation | Shen et al. (98) |
| Cigarette smoke extract (CSE) treatment of lung fibroblasts | Emphysema caused by cigarette smoke induces the expression of MMP-2 and MT1-MMP via the EGR1 signaling pathway | Ning et al. (96) |
| Cigarette smoke induced HBE and BEAS-2B in patients with COPD | In vitro and in vivo exposure of lung epithelial cells to cigarette smoke EGR1 mediates E2F to promote autophagy and apoptosis | Chen et al. (99) |
| Cigarette smoke induced NL9 cells | An inflammatory factor and chemokine pathway is activated by tobacco smoke by MAPK–EGR1–HSP70 | Li et al. (100) |
| CSE-stimulated lung epithelial cells A549 and mouse lung | High expression of CSE proinflammatory EGR1 further mediates elevated expression of inflammatory factors IL-1β and TNF-α, exacerbating airway inflammation | Reynolds et al. (94) |
| CSE stimulates HBE | CSE promotes the interaction of EGR1 and AP-1 to further mediate the expression of the target gene MUC5AC, a key molecule regulating mucus production in the airway epithelium | Wang et al. (101) |
| Lung tissue from patients undergoing lung surgery for advanced emphysema | EGR1 is persistently upregulated in advanced emphysema and regulates genes associated with the pathophysiological progression of emphysema | Zhang et al. (95) |
| Bioinformatics analysis | Ning et al. (92); Huang et al. (93) | |
| CSE in epithelial (rat ATI cell lines R3/1 and A549) and macrophage (RAW264.7) cell lines | Positive feedback mechanism between Egr-1 and RAGE promotes sustained high expression of RAGE during cigarette smoke exposure | Reynolds et al. (103) |
| One hundred fifty-one male smoking patients with COPD and 100 male smoking controls | Having the G allele of the Egr-1 gene polymorphism increases the risk of COPD | Chen et al. (80) |
| Cigarette smoke condensate (CSC) induces BEAS-2B | FH535 increases CSC-induced cytotoxicity and inhibits EGR1 expression, but does not affect EGR-1 nuclear accumulation | Polk (104) |
| Cigarette smoke stimulation BEAS-2B | CS induces EGR1 expression via AHR, leading to apoptosis | Hattori et al. (102) |
AHR, aryl hydrocarbon receptor; BEAS-2B, bronchial epithelium transformed with Ad12-SV40 2B; COPD, chronic obstructive pulmonary disease; EGR1, early growth response 1; ERK, extracellular signal-regulated kinase; GGPPS, geranylgeranyl diphosphate synthase; HBE, human bronchial epithelium; IL-1β, interleukin-1 beta; MAPK, mitogen-activated protein kinase; MMP-2, matrix metalloproteinase-2, MT1-MMP, membrane type 1 matrix metalloproteinase; PIGF, placental growth factor; TNF-α, tumor necrosis factor-alpha.