Cannabinoid receptors 1 and 2 oppositely regulate epidermal permeability barrier status and differentiation

Exp Dermatol. 2012 Sep;21(9):688-93. doi: 10.1111/j.1600-0625.2012.01561.x.


Cannabinoid receptors (CBR) 1 and 2 have been implicated in keratinocyte differentiation/proliferation. How CB receptors affect epidermal permeability barrier and stratum corneum structure and function remains unclear. Permeability barrier abrogation was induced by sequential tape-stripping of the SC and assessed in both CB1R and CB2R knockout (-/-) mice in comparison with wild-type (+/+) littermates. Absence of CB1R delays permeability barrier recovery, while the latter was found to be accelerated in CB2R -/- mice. While increased lamellar body (LB) secretion is observed in CB2R -/- mice accounting for the enhanced recovery, CB1R -/- animals display strong alterations in lipid bilayer structures. Markers for epidermal differentiation (i.e. filaggrin, loricrin and involucrin) and terminal differentiation (i.e. TUNEL assay and caspase-14 activation) were respectively decreased and increased in CB1R and CB2R -/- mice. Surprisingly, CB1R agonist treatment of human cultured keratinocytes increases mRNA of p21 and cytokeratin 1 and 10 and decreases cyclin D1 but protein levels remained unchanged. Such paradox could partially be explained by the increase in non-phosphorylated-4E-BP1, an inhibitor of mRNA translation, following CB1R agonist treatment. Altogether, these observations put forward the importance and the complexity of cannabinoid signalling for the regulation of permeability barrier and epidermal differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Apoptosis
  • Carrier Proteins / metabolism*
  • Caspase 14 / metabolism
  • Cell Cycle Proteins
  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Cyclin D / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Eukaryotic Initiation Factors
  • Filaggrin Proteins
  • Humans
  • In Situ Nick-End Labeling
  • Keratin-1 / metabolism
  • Keratin-10 / metabolism
  • Keratinocytes / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Permeability
  • Phosphoproteins / metabolism*
  • RNA, Messenger / metabolism
  • Receptor, Cannabinoid, CB1 / antagonists & inhibitors
  • Receptor, Cannabinoid, CB1 / genetics
  • Receptor, Cannabinoid, CB1 / metabolism*
  • Receptor, Cannabinoid, CB2 / genetics
  • Receptor, Cannabinoid, CB2 / metabolism*
  • Signal Transduction
  • Skin / cytology
  • Skin / metabolism*
  • Water / metabolism*


  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Cell Cycle Proteins
  • Cnr2 protein, mouse
  • Cyclin D
  • Cyclin-Dependent Kinase Inhibitor p21
  • Eif4ebp1 protein, mouse
  • Eukaryotic Initiation Factors
  • FLG protein, human
  • Filaggrin Proteins
  • Keratin-1
  • Phosphoproteins
  • RNA, Messenger
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2
  • Water
  • Keratin-10
  • Caspase 14