ArticleThe Journal of biological chemistry2008
Inflammatory levels of nitric oxide inhibit airway epithelial cell migration by inhibition of the kinase ERK1/2 and activation of hypoxia-inducible factor-1 alpha.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 46 citations in OpenAlex.
- Hypoxia: a critical pathophysiological driver in respiratory inflammatory diseases.Military Medical Research · 2026Review
- Decoding the HIF-1-driven metabolic-inflammatory-immune axis in sepsis-associated lung injury: a comprehensive overview.Frontiers in immunology · 2025Review
- The reduced SCFA-producing gut microbes are involved in the inflammatory activation in Kawasaki disease.Frontiers in immunology · 2023Article
- A novel imidazolinone metformin-methylglyoxal metabolite promotes endothelial cell angiogenesis via the eNOS/HIF-1α pathway.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Celecoxib suppresses cutaneous squamous-cell carcinoma cell migration via inhibition of SDF1-induced endocytosis of CXCR4.OncoTargets and therapy · 2018Article
- G-protein-coupled receptor kinase-2 is a critical regulator of TNFα signaling in colon epithelial cells.The Biochemical journal · 2017Article
- PTEN regulates lung endodermal morphogenesis through MEK/ERK pathway.Developmental biology · 2015Article
- Nitric oxide donors increase PVR/CD155 DNAM-1 ligand expression in multiple myeloma cells: role of DNA damage response activation.BMC cancer · 2015Article
- Promoting endothelial function by S-nitrosoglutathione through the HIF-1α/VEGF pathway stimulates neurorepair and functional recovery following experimental stroke in rats.Drug design, development and therapy · 2015Article
- Effects of hypoxia-inducible factor-1α silencing on the proliferation of CBRH-7919 hepatoma cells.World journal of gastroenterology · 2013Article
- Dual oxidase-1 is required for airway epithelial cell migration and bronchiolar reepithelialization after injury.American journal of respiratory cell and molecular biology · 2013Article
- Human indoleamine 2,3-dioxygenase is a catalyst of physiological heme peroxidase reactions: implications for the inhibition of dioxygenase activity by hydrogen peroxide.The Journal of biological chemistry · 2013Article
- Nitric oxide-dependent downregulation of BRCA1 expression promotes genetic instability.Cancer research · 2013Article
- Knowledge translation: airway epithelial cell migration and respiratory diseases.Cellular and molecular life sciences : CMLS · 2012Review
- Keratin 8 phosphorylation regulates keratin reorganization and migration of epithelial tumor cells.Journal of cell science · 2012Article
- Activation of hypoxia-inducible factor-1 protects airway epithelium against oxidant-induced barrier dysfunction.American journal of physiology. Lung cellular and molecular physiology · 2011Article
- Activation of the glutaredoxin-1 gene by nuclear factor κB enhances signaling.Free radical biology & medicine · 2011Article
- Interactions between nitric oxide and hypoxia-inducible factor signaling pathways in inflammatory disease.Nitric oxide : biology and chemistry · 2011Review
- Modulation of NF-κB and hypoxia-inducible factor--1 by S-nitrosoglutathione does not alter allergic airway inflammation in mice.American journal of respiratory cell and molecular biology · 2011Article
- Nitric oxide induces HIF-1α stabilization and expression of intestinal trefoil factor in the damaged rat jejunum and modulates ulcer healing.Journal of gastroenterology · 2011Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Increased synthesis of NO during airway inflammation, caused by induction of nitric-oxide synthase 2 in several lung cell types, may contribute to epithelial injury and permeability. To investigate the consequence of elevated NO production on epithelial function, we exposed cultured monolayers of human bronchial epithelial cells to the NO donor diethylenetriaamine NONOate. At concentrations generating high nanomolar levels of NO, representative of inflammatory conditions, diethylenetriaamine NONOate markedly reduced wound closure in an in vitro scratch injury model, primarily by inhibiting epithelial cell migration. Analysis of signaling pathways and gene expression profiles indicated a rapid induction of the mitogen-activated protein kinase phosphatase (MPK)-1 and decrease in extracellular signal-regulated kinase (ERK)1/2 activation, as well as marked stabilization of hypoxia-inducible factor (HIF)-1alpha and activation of hypoxia-responsive genes, under these conditions. Inhibition of ERK1/2 signaling using U0126 enhanced HIF-1alpha stabilization, implicating ERK1/2 dephosphorylation as a contributing mechanism in NO-mediated HIF-1alpha activation. Activation of HIF-1alpha by the hypoxia mimic cobalt chloride, or cell transfection with a degradation-resistant HIF-1alpha mutant construct inhibited epithelial wound repair, implicating HIF-1alpha in NO-mediated inhibition of cell migration. Conversely, NO-mediated inhibition of epithelial wound closure was largely prevented after small interfering RNA suppression of HIF-1alpha. Finally, NO-mediated inhibition of cell migration was associated with HIF-1alpha-dependent induction of PAI-1 and activation of p53, both negative regulators of epithelial cell migration. Collectively, our results demonstrate that inflammatory levels of NO inhibit epithelial cell migration, because of suppression of ERK1/2 signaling, and activation of HIF-1alpha and p53, with potential consequences for epithelial repair and remodeling during airway inflammation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.