Tumor necrosis factor-α coordinates with transforming growth factor-β1 to induce epithelial-mesenchymal transition and migration via the NF-κB/NOX4 pathway in bronchial epithelial cells

Mol Biol Rep. 2022 Aug 1. doi: 10.1007/s11033-022-07777-4. Online ahead of print.


BACKGROUND: Epithelial-to-mesenchymal transition (EMT) is the process by which epithelial cells transform into mesenchymal cells, which plays a significant role in lung fibrotic disease. Transforming growth factor-β1(TGF-β1) is considered to be the most effective EMT inducer. The purpose of this study was to investigate the effect of the proinflammatory cytokine tumor necrosis factor-α (TNF-α) on TGF-β1-induced EMT and the underlying mechanisms in the human bronchial epithelial cell line BEAS-2B.

METHODS: Human bronchial epithelial BEAS-2B cells were treated with TGF-β1 and TNF-α separately or in combination for 24 h, and qRT-PCR, western blotting, immunofluorescence staining, and migration assays were used to investigate the EMT process. Moreover, to further explore the effect of the NF-κB pathway on the EMT process, inhibitor assays (BAY-117082, NF-κB inhibitor), wound healing assays, and western blotting were performed.

RESULTS: The results showed that both cytokines enhanced the transformation of BEAS-2B cells from epithelial to mesenchymal cells. In addition, combined treatment with TNF-α and TGF-β1 further reduced E-cadherin expression, which conversely elevated α-SMA and vimentin mRNA and protein levels. Correspondingly, the migration rate of BEAS-2B cells was also increased. Furthermore, inhibiting the NF-κB signaling pathway blocked the expression of EMT-related markers and NOX4 induced by TGF-β1 and TNF-α, as well as cell migration.

CONCLUSION: Taken together, TNF-α and TGF-β1 cooperatively promoted EMT and cell migration in BEAS-2B cells through the NF-κB/NOX4 signaling pathway.

PMID:35913579 | DOI:10.1007/s11033-022-07777-4

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