ArticleScientific reports2019
NRF2-dependent gene expression promotes ciliogenesis and Hedgehog signaling.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- TSLP impairs mucociliary transport by inhibiting JAK signaling in both central and peripheral airways.Pflugers Archiv : European journal of physiology · 2026Article
- Transcriptomic and functional responses of human airway cells to vaped ∆8-THC and its oxidation product ∆8-THCQ.Scientific reports · 2026Article
- Multifaceted role of primary cilia and ciliary proteins: A potential nexus for hedgehog signaling and prostate cancer.Biochimica et biophysica acta. Molecular basis of disease · 2026Review
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- Article
- The primary cilium-autophagy axis in vascular homeostasis and cardiovascular disease: mechanistic crosstalk and evidence boundaries.Frontiers in cardiovascular medicine · 2026Review
- Emerging roles of the ciliary-mitochondrial axis in cellular homeostasis and neuroprotection.Molecular neurodegeneration advances · 2025Article
- The senescence-associated secretome of Hedgehog-deficient hepatocytes drives MASLD progression.The Journal of clinical investigation · 2024Article
- Oxidative Stress Induces Skin Pigmentation in Melasma by Inhibiting Hedgehog Signaling.Antioxidants (Basel, Switzerland) · 2023Article
- The Transcription Factor NRF2 Has Epigenetic Regulatory Functions Modulating HDACs, DNMTs, and miRNA Biogenesis.Antioxidants (Basel, Switzerland) · 2023Article
- EVC-EVC2 complex stability and ciliary targeting are regulated by modification with ubiquitin and SUMO.Frontiers in cell and developmental biology · 2023Article
- Article
- Pathophysiology of Primary Cilia: Signaling and Proteostasis Regulation.Frontiers in cell and developmental biology · 2022Review
- Keap1/Nrf2 Signaling Pathway.Antioxidants (Basel, Switzerland) · 2021Article
- Article
- Nrf2-A Molecular Target for Sepsis Patients in Critical Care.Biomolecules · 2020Review
- NRF2 and the Ambiguous Consequences of Its Activation during Initiation and the Subsequent Stages of Tumourigenesis.Cancers · 2020Review
- The Potential Role and Regulatory Mechanisms of MUC5AC in Chronic Obstructive Pulmonary Disease.Molecules (Basel, Switzerland) · 2020Review
- NRF2 and Primary Cilia: An Emerging Partnership.Antioxidants (Basel, Switzerland) · 2020Review
- NRF2 negatively regulates primary ciliogenesis and hedgehog signaling.PLoS biology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transcription factor NRF2 is a master regulator of cellular antioxidant and detoxification responses, but it also regulates other processes such as autophagy and pluripotency. In human embryonic stem cells (hESCs), NRF2 antagonizes neuroectoderm differentiation, which only occurs after NRF2 is repressed via a Primary Cilia-Autophagy-NRF2 (PAN) axis. However, the functional connections between NRF2 and primary cilia, microtubule-based plasma membrane protrusions that function as cellular antennae, remain poorly understood. For instance, nothing is known about whether NRF2 affects cilia, or whether cilia regulation of NRF2 extends beyond hESCs. Here, we show that NRF2 and primary cilia reciprocally regulate each other. First, we demonstrate that fibroblasts lacking primary cilia have higher NRF2 activity, which is rescued by autophagy-activating mTOR inhibitors, indicating that the PAN axis also operates in differentiated cells. Furthermore, NRF2 controls cilia formation and function. NRF2-null cells grow fewer and shorter cilia and display impaired Hedgehog signaling, a cilia-dependent pathway. These defects are not due to increased oxidative stress or ciliophagy, but rather to NRF2 promoting expression of multiple ciliogenic and Hedgehog pathway genes. Among these, we focused on GLI2 and GLI3, the transcription factors controlling Hh pathway output. Both their mRNA and protein levels are reduced in NRF2-null cells, consistent with their gene promoters containing consensus ARE sequences predicted to bind NRF2. Moreover, GLI2 and GLI3 fail to accumulate at the ciliary tip of NRF2-null cells upon Hh pathway activation. Given the importance of NRF2 and ciliary signaling in human disease, our data may have important biomedical implications.
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Registered trials
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