ArticleRespiratory research2012
Gene expression profiling following NRF2 and KEAP1 siRNA knockdown in human lung fibroblasts identifies CCL11/Eotaxin-1 as a novel NRF2 regulated gene.
Article in Respiratory research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 35 citations in OpenAlex.
- CHAC1-linked NRF2 protein expression participates in pancreatic islet protection by dextrorphan.iScience · 2026Article
- Hydrogen sulfide (H2S) coordinates redox balance, carbon metabolism, and mitochondrial bioenergetics to suppress SARS-CoV-2 infection.PLoS pathogens · 2025Article
- CCL11 (Eotaxin) Promotes the Advancement of Aging-Related Cardiovascular Diseases.Reviews in cardiovascular medicine · 2025Review
- Research on the Anti-Fatigue Effects and Mechanisms of Arecoline in Sleep-Deprived Mice.Nutrients · 2024Article
- Characterization of early psychosis patients carrying a genetic vulnerability to redox dysregulation: a computational analysis of mechanism-based gene expression profile in fibroblasts.Molecular psychiatry · 2023Article
- Dimethyl Fumarate, an Approved Multiple Sclerosis Treatment, Reduces Brain Oxidative Stress in SIV-Infected Rhesus Macaques: Potential Therapeutic Repurposing for HIV Neuroprotection.Antioxidants (Basel, Switzerland) · 2021Article
- MicroRNA and ROS Crosstalk in Cardiac and Pulmonary Diseases.International journal of molecular sciences · 2020Review
- Primary Amine Modified Gold Nanodots Regulate Macrophage Function and Antioxidant Response: Potential Therapeutics Targeting of Nrf2.International journal of nanomedicine · 2020Article
- Signaling Pathways, Chemical and Biological Modulators of Nucleotide Excision Repair: The Faithful Shield against UV Genotoxicity.Oxidative medicine and cellular longevity · 2019Review
- Bioengineered NRF2-siRNA Is Effective to Interfere with NRF2 Pathways and Improve Chemosensitivity of Human Cancer Cells.Drug metabolism and disposition: the biological fate of chemicals · 2018Article
- MicroRNA miR-24-3p Reduces Apoptosis and Regulates Keap1-Nrf2 Pathway in Mouse Cardiomyocytes Responding to Ischemia/Reperfusion Injury.Oxidative medicine and cellular longevity · 2018Article
- Nrf2 exerts cell-autonomous antifibrotic effects: compromised function in systemic sclerosis and therapeutic rescue with a novel heterocyclic chalcone derivative.Translational research : the journal of laboratory and clinical medicine · 2017Article
- Progression inference for somatic mutations in cancer.Heliyon · 2017Article
- Probucol Protects Rats from Cardiac Dysfunction Induced by Oxidative Stress following Cardiopulmonary Resuscitation.Oxidative medicine and cellular longevity · 2017Article
- Aerosol Delivery of siRNA to the Lungs. Part 2: Nanocarrier-based Delivery Systems.Kona : powder science and technology in Japan · 2017Article
- Chronic obstructive pulmonary disease candidate gene prioritization based on metabolic networks and functional information.PloS one · 2017Article
- The role of transcription factor Nrf2 in skin cells metabolism.Archives of dermatological research · 2015Review
- Compromised peroxisomes in idiopathic pulmonary fibrosis, a vicious cycle inducing a higher fibrotic response via TGF-β signaling.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- siRNA delivery to the lung: what's new?Advanced drug delivery reviews · 2014Review
- The clinical potential of influencing Nrf2 signaling in degenerative and immunological disorders.Clinical pharmacology : advances and applications · 2014Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOxidative Stress contributes to the pathogenesis of many diseases. The NRF2/KEAP1 axis is a key transcriptional regulator of the anti-oxidant response in cells. Nrf2 knockout mice have implicated this pathway in regulating inflammatory airway diseases such as asthma and COPD. To better understand the role the NRF2 pathway has on respiratory disease we have taken a novel approach to define NRF2 dependent gene expression in a relevant lung system.
methodsNormal human lung fibroblasts were transfected with siRNA specific for NRF2 or KEAP1. Gene expression changes were measured at 30 and 48 hours using a custom Affymetrix Gene array. Changes in Eotaxin-1 gene expression and protein secretion were further measured under various inflammatory conditions with siRNAs and pharmacological tools.
resultsAn anti-correlated gene set (inversely regulated by NRF2 and KEAP1 RNAi) that reflects specific NRF2 regulated genes was identified. Gene annotations show that NRF2-mediated oxidative stress response is the most significantly regulated pathway, followed by heme metabolism, metabolism of xenobiotics by Cytochrome P450 and O-glycan biosynthesis. Unexpectedly the key eosinophil chemokine Eotaxin-1/CCL11 was found to be up-regulated when NRF2 was inhibited and down-regulated when KEAP1 was inhibited. This transcriptional regulation leads to modulation of Eotaxin-1 secretion from human lung fibroblasts under basal and inflammatory conditions, and is specific to Eotaxin-1 as NRF2 or KEAP1 knockdown had no effect on the secretion of a set of other chemokines and cytokines. Furthermore, the known NRF2 small molecule activators CDDO and Sulphoraphane can also dose dependently inhibit Eotaxin-1 release from human lung fibroblasts.
conclusionsThese data uncover a previously unknown role for NRF2 in regulating Eotaxin-1 expression and further the mechanistic understanding of this pathway in modulating inflammatory lung disease.
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