Please use this identifier to cite or link to this item: http://hdl.handle.net/10668/4115
Title: Cannabidiol induces antioxidant pathways in keratinocytes by targeting BACH1
Authors: Casares, Laura
García, Víctor
Garrido-Rodríguez, Martín
Millán, Estrella
Collado, Juan A.
García-Martín, Adela
Peñarando, Jon
Calzado, Marco A.
de la Vega, Laureano
Muñoz, Eduardo
metadata.dc.contributor.authoraffiliation: [Casares,L; de la Vega,L] Jacqui Wood Cancer Centre, Division of Cellular Medicine, School of Medicine, University of Dundee, Dundee, Scotland, UK. [García,V; Garrido-Rodríguez,M; Millán,E; Collado,JA] Innohealth Group, Madrid, Spain. [García,V; Garrido-Rodríguez,M; Collado,JA; Calzado,MA; Muñoz,E] Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain. [García-Martín,A; Peñarando,J] Emerald Health Biotechnology, Córdoba, Spain. [Calzado,MA; Muñoz,E] Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Spain. [Calzado,MA; Muñoz,E] Hospital Universitario Reina Sofía, Córdoba, Spain.
Keywords: Cannabidiol;BACH1;HMOX1;NRF2;Keratinocytes;Queratinocitos
metadata.dc.subject.mesh: Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Antioxidants
Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Transcription Factors::Basic-Leucine Zipper Transcription Factors
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Terpenes::Cannabinoids::Cannabidiol
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Differentiation
Medical Subject Headings::Anatomy::Cells::Cells, Cultured
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Oxygenases::Mixed Function Oxygenases::Heme Oxygenase (Decyclizing)::Heme Oxygenase-1
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Sequence Analysis::High-Throughput Nucleotide Sequencing
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Anatomy::Cells::Epithelial Cells::Keratinocytes
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Mass Spectrometry
Medical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Proteolysis
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Sequence Analysis::Sequence Analysis, RNA
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Signal Transduction
Issue Date: 5-Sep-2019
Publisher: Elsevier
Citation: Casares L, García V, Garrido-Rodríguez M, Millán E, Collado JA, García-Martín A, et al. Cannabidiol induces antioxidant pathways in keratinocytes by targeting BACH1. Redox Biol. 2020 Jan;28:101321
Abstract: Cannabidiol (CBD) is a major non-psychotropic phytocannabinoid that attracted a great attention for its therapeutic potential against different pathologies including skin diseases. However, although the efficacy in preclinical models and the clinical benefits of CBD in humans have been extensively demonstrated, the molecular mechanism(s) and targets responsible for these effects are as yet unknown. Herein we characterized at the molecular level the effects of CBD on primary human keratinocytes using a combination of RNA sequencing (RNA-Seq) and sequential window acquisition of all theoretical mass spectrometry (SWATH-MS). Functional analysis revealed that CBD regulated pathways involved in keratinocyte differentiation, skin development and epidermal cell differentiation among other processes. In addition, CBD induced the expression of several NRF2 target genes, with heme oxygenase 1 (HMOX1) being the gene and the protein most upregulated by CBD. CRISPR/Cas9-mediated genome editing, RNA interference and biochemical studies demonstrated that the induction of HMOX1 mediated by CBD, involved nuclear export and proteasomal degradation of the transcriptional repressor BACH1. Notably, we showed that the effect of BACH1 on HMOX1 expression in keratinocytes is independent of NRF2. In vivo studies showed that topical CBD increased the levels of HMOX1 and of the proliferation and wound-repair associated keratins 16 and 17 in the skin of mice. Altogether, our study identifies BACH1 as a molecular target for CBD in keratinocytes and sets the basis for the use of topical CBD for the treatment of different skin diseases including atopic dermatitis and keratin disorders.
URI: http://hdl.handle.net/10668/4115
metadata.dc.relation.publisherversion: https://www.sciencedirect.com/science/article/pii/S2213231719306470?via%3Dihub
metadata.dc.identifier.doi: 10.1016/j.redox.2019.101321
ISSN: 2213-2317 (Online)
Appears in Collections:01- Artículos - Hospital Reina Sofía
01- Artículos - IMIBIC. Instituto Maimónides de Investigación Biomédica de Córdoba

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