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

Overview

Journal Mol Biol Rep

Specialty Molecular Biology

Date 2022 Aug 1

PMID 35913579

Authors

Ke Li

Rong Zhou

Mingze Ma

Chaomei Jin

Linlin Jiao

Siyu Zhang

Mei Tian

Fang Zhou

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Pentoxifylline Inhibits TNF-α/TGF-β1-Induced Epithelial-Mesenchymal Transition via Suppressing the NF-κB Pathway and Expression in CaSki Cells.

Palafox-Mariscal L, Ortiz-Lazareno P, Jave-Suarez L, Aguilar-Lemarroy A, Villasenor-Garcia M, Cruz-Lozano J Int J Mol Sci. 2023; 24(13).

PMID: 37445768 PMC: 10342099. DOI: 10.3390/ijms241310592.

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