Blockage of TGF-α Induced by Spherical Silica Nanoparticles Inhibits Epithelial-Mesenchymal Transition and Proliferation of Human Lung Epithelial Cells

Abstract

Background. Xuanwei City in Yunnan province has been one of the towns with highest lung cancer mortality in China. The high content of amorphous silica in the bituminous coal from Xuanwei of Yunnan is mainly present as irregular and spherical silica nanoparticles (SiNPs). It has been reported that silica nanoparticles in bituminous coal correlated with the high incidence of lung cancer in Xuanwei. To explore the role and mechanism of SiNPs in the tumorigenesis of lung cancer in Xuanwei, human mononuclear cells (THP-1) and human bronchial epithelial cells (BEAS-2B) were cocultured in a transwell chamber. Combined with Benzo[a]pyrene-7, 8-dihydrodiol-9, and 10-epoxide (BPDE), SiNPs could significantly promote the proliferation and Epithelial-Mesenchymal Transition (EMT) and inhibit apoptosis of BEAS-2B cells and induce the release of TGF-α from THP-1 cells. After neutralizing TGF-α with antibody, the proliferation and EMT were decreased and enhanced apoptosis of BEAS-2B cells. Furthermore, the results showed that TGF-α in the sera of patients with lung adenocarcinoma in Xuanwei were significantly higher than in patients with benign pulmonary lesions in Xuanwei and those with lung adenocarcinoma in outside of Xuanwei of Yunnan. Taken together, our study found that SiNPs promoted the proliferation and EMT of BEAS-2B cells by inducing the release of TGF-α from THP-1 cells.

p62/SQSTM1 accumulation due to degradation inhibition and transcriptional activation plays a critical role in silica nanoparticle-induced airway inflammation via NF-κB activation

“…In the present study, we assessed the role of p62 accumulation in SiNP-triggered airway inflammation. Once inhaled, SiNPs could stimulate apoptosis, oxidative stress, and the epithelial to mesenchymal transition (EMT) in addition to inflammation [3,5,37]. Interestingly, these cellular outcomes, including the EMT, are also mediated by p62 accumulation [38].…”

Characterization of the soft-tissue wall lining residual periodontal pockets and implications in periodontal wound healing

“…The TGF-α and TGF-β1 are important growth factors in periodontal healing but they have distinct biological roles. Transforming Growth Factor-alpha acts as a ligand for the epidermal growth factor receptor (EGFR), triggering cell proliferation, differentiation, and development [31]. Transforming Growth Factor-beta-1 promotes the production of GT by enhancing the expression of extracellular matrix (ECM)-related genes such as bronectin, bronectin receptor, collagen, and protease inhibitors [32].…”

MiR-205 suppressed the malignant behaviors of breast cancer cells by targeting CLDN11 via modulation of the epithelial-to-mesenchymal transition

“…After the transfection of miR-205 mimics or control, 1.0×10 4 cells were seeded into 96-well plates containing cells 100 μl complete medium [ 40 ]. After incubation with 10 μ l CCK for 30 minutes at 37° C, the absorbance was measured at 450 nm using a microplate reader [ 41 ]. All experiments were independently performed in triplicate.…”