ArticleThe Journal of biological chemistry2018
The NFκB subunit RELA is a master transcriptional regulator of the committed epithelial-mesenchymal transition in airway epithelial cells.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 67 citations in OpenAlex.
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- Spatial transcriptomics reveals molecular differences associated with malignant transformation in oral epithelial dysplasia.Frontiers in immunology · 2026Article
- MicroRNA 196a contributes to the aggressiveness of esophageal adenocarcinoma through the MYC/TERT/NFκB axis.Molecular oncology · 2025Article
- An RGD motif on SARS-CoV-2 Spike induces TGF-β signaling and downregulates interferon.Journal of virology · 2025Article
- An orally bioavailable BRD4 inhibitor disrupts expansion of a pathogenic epithelial-mesenchymal niche in bleomycin-induced fibrosis.Respiratory research · 2025Article
- Molecular Study from the Signaling Pathways of Four PotentialInternational journal of molecular sciences · 2025Article
- Mechanisms on How Matricellular Microenvironments Sustain Idiopathic Pulmonary Fibrosis.International journal of molecular sciences · 2025Review
- SMARCA4 regulates inducible BRD4 genomic redistribution coupling intrinsic immunity and plasticity in epithelial injury-repair.Nucleic acids research · 2025Article
- Article
- Alveolar epithelial cell dysfunction and epithelial-mesenchymal transition in pulmonary fibrosis pathogenesis.Frontiers in molecular biosciences · 2025Review
- Interactions between epithelial mesenchymal plasticity, barrier dysfunction and innate immune pathways shape the genesis of allergic airway disease.Expert review of respiratory medicine · 2025Review
- NF-κB/RelA signaling in secretoglobin progenitors mediates plasticity and MMP-induced barrier disruption in house dust mite-induced allergic asthma.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- GLUT3-mediated cigarette smoke-induced epithelial-mesenchymal transition in chronic obstructive pulmonary disease through the NF-kB/ZEB1 pathway.Respiratory research · 2024Article
- Cooperative interaction of interferon regulatory factor -1 and bromodomain-containing protein 4 on RNA polymerase activation for intrinsic innate immunity.Frontiers in immunology · 2024Article
- Impact of particulate air pollution on airway injury and epithelial plasticity; underlying mechanisms.Frontiers in immunology · 2024Review
- Copy number gain of ACTN4 is associated with poor prognosis in patients with upper urinary tract urothelial carcinoma.Cancer science · 2023Article
- Genomic targets of the IRE1-XBP1s pathway in mediating metabolic adaptation in epithelial plasticity.Nucleic acids research · 2023Article
- 8-Oxoguanine targeted by 8-oxoguanine DNA glycosylase 1 (OGG1) is central to fibrogenic gene activation upon lung injury.Nucleic acids research · 2023Article
- xcore: an R package for inference of gene expression regulators.BMC bioinformatics · 2023Article
- Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The epithelial-mesenchymal transition (EMT) is a multistep dedifferentiation program important in tissue repair. Here, we examined the role of the transcriptional regulator NF-κB in EMT of primary human small airway epithelial cells (hSAECs). Surprisingly, transforming growth factor β (TGFβ) activated NF-κB/RELA proto-oncogene, NF-κB subunit (RELA) translocation within 1 day of stimulation, yet induction of its downstream gene regulatory network occurred only after 3 days. A time course of TGFβ-induced EMT transition was analyzed by RNA-Seq in the absence or presence of inducible shRNA-mediated silencing of RELA. In WT cells, TGFβ stimulation significantly affected the expression of 2,441 genes. Gene set enrichment analysis identified WNT, cadherin, and NF-κB signaling as the most prominent TGFβ-inducible pathways. By comparison, RELA controlled expression of 3,138 overlapping genes mapping to WNT, cadherin, and chemokine signaling pathways. Conducting upstream regulator analysis, we found that RELA controls six clusters of upstream transcription factors, many of which overlapped with a transcription factor topology map of EMT developed earlier. RELA triggered expression of three key EMT pathways: 1) the WNT/β-catenin morphogen pathway, 2) the JUN transcription factor, and 3) the Snail family transcriptional repressor 1 (SNAI1). RELA binding to target genes was confirmed by ChIP. Experiments independently validating WNT dependence on RELA were performed by silencing RELA via genome editing and indicated that TGFβ-induced
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