ArticleAntioxidants (Basel, Switzerland)2024
Induction of Semaphorin 3A by Resveratrol and Pinostilbene via Activation of the AHR-NRF2 Axis in Human Keratinocytes.
Article in Antioxidants (Basel, Switzerland), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- The Therapeutic Potential of Polyphenols in Modulating Barrier Lipids, Microbiome Interactions, and Inflammatory Pathways in Atopic Dermatitis.Nutrients · 2026Review
- Neuron-Derived Sema3B Facilitates Microglial Hematoma Clearance After Intracerebral Hemorrhage.Antioxidants (Basel, Switzerland) · 2026Article
- Resveratrol Analogs Ameliorate Mitochondrial Impairment and Insulin Resistance in a Streptozotocin-Induced In Vitro Model of Alzheimer's Disease.International journal of molecular sciences · 2025Article
- Advances in Atopic Dermatitis Treatment: From Pathogenesis to Natural Product-Based Therapies.Phytotherapy research : PTR · 2025Review
- Resveratrol in Dermatological Therapy: A Critical Review of Mechanisms, Delivery Innovations, and Clinical Frontiers.Clinical, cosmetic and investigational dermatology · 2025Review
- Mast cell-neuron axis as a core mechanism in chronic pruritus of atopic dermatitis: from mechanistic insights to therapeutic targets.Frontiers in immunology · 2025Review
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Authors and funding
5 authors.
Funding
Abstract
Semaphorin 3A (SEMA3A), a nerve-repellent factor produced by keratinocytes, has an inhibitory effect on nerve extension to the epidermis. Epidermal innervation is involved in pruritus in inflammatory skin diseases such as atopic dermatitis (AD) and dry skin. We previously reported that tapinarof, a stilbene molecule, upregulates SEMA3A in human keratinocytes. We also showed that this mechanism is mediated via the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, and the nuclear factor erythroid 2-related factor 2 (NRF2) axis. Since some stilbenes activate AHR and NRF2, we attempted to identify other stilbenes that upregulate SEMA3A. We analyzed normal human epidermal keratinocytes (NHEKs) treated with 11 types of stilbenes and examined SEMA3A expression. We found that resveratrol and pinostilbene, antioxidant polyphenols, upregulated SEMA3A and increased nuclear AHR and NRF2 expression. In addition, AHR knockdown by small interfering RNA (siRNA) transfection abolished the NRF2 nuclear expression. Furthermore, AHR and NRF2 knockdown by siRNA transfection abrogated resveratrol- and pinostilbene-induced SEMA3A upregulation. Finally, we confirmed that resveratrol and pinostilbene increased SEMA3A promoter activity through NRF2 binding using ChIP-qPCR analysis. These results suggest that resveratrol and pinostilbene upregulate SEMA3A via the AHR-NRF2 axis in human keratinocytes.
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