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Canna~Fangled Abstracts

Epigenetic Control of Skin Differentiation Genes by Phytocannabinoids.

By July 23, 2013No Comments

pm2Epigenetic Control of Skin Differentiation Genes by Phytocannabinoids.


Department of Biomedical Sciences, University of Teramo, Teramo, Italy.



A role for endocannabinoid signaling has been reported in the control of epidermal physiology, whereby anandamide is able to regulate the expression of skin differentiation genes through DNA methylation. Here, we have investigated the possible epigenetic regulation of these genes by selected phytocannabinoids, plant-derived cannabinoids holding potential as novel therapeutics for various human diseases.


The effects of cannabidiol, cannabigerol and cannabidivarin were investigated in human keratinocytes (HaCaT cells) on the expression of the skin differentiation genes keratins 1 and 10, involucrin and transglutaminase 5, as well as on DNA methylation of keratin 10 gene. Moreover, changes induced by phytocannabinoids in global DNA methylation and in the activity and expression of four major DNA methyltransferases (DNMT1, 3a, 3b and 3L) were studied.


Treatment of differentiated HaCaT cells with cannabidiol or cannabigerol significantly reduced the expression of all genes tested via increased DNA methylation for keratin 10 gene; instead, cannabidivarin was ineffective. Remarkably, cannabidiol reduced keratin 10 mRNA through a type-1 cannabinoid (CB1 ) receptor-dependent mechanism, whereas cannabigerol did not engage CB1 nor type-2 cannabinoid (CB2 ) receptors of HaCaT cells. In addition cannabidiol, but not cannabigerol, increased global DNA methylation levels by selectively enhancing DNMT1 expression, without affecting DNMT 3a, 3b or 3L.


These findings identify the phytocannabinoids cannabidiol and cannabigerol as transcriptional repressors that can control cell proliferation and differentiation, suggesting (especially for cannabidiol) a possible exploitation as lead compounds to be used in the development of novel therapeutics for skin diseases.
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DNA methylation, Phytocannabinoids, endocannabionid system, gene expression, skin


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