| First Author | Tu CL | Year | 2012 |
| Journal | J Invest Dermatol | Volume | 132 |
| Issue | 10 | Pages | 2350-2359 |
| PubMed ID | 22622426 | Mgi Jnum | J:189566 |
| Mgi Id | MGI:5446115 | Doi | 10.1038/jid.2012.159 |
| Citation | Tu CL, et al. (2012) Ablation of the calcium-sensing receptor in keratinocytes impairs epidermal differentiation and barrier function. J Invest Dermatol 132(10):2350-9 |
| abstractText | The calcium-sensing receptor (CaR) has an essential role in mediating Ca(2+)-induced keratinocyte differentiation in vitro. In this study, we generated keratinocyte-specific CaR knockout ((Epid)CaR(-/-)) mice to investigate the function of the CaR in epidermal development in vivo. (Epid)CaR(-/-) mice exhibited a delay in permeability barrier formation during embryonic development. Ion capture cytochemistry detected the loss of the epidermal Ca(2+) gradient in the (Epid)CaR(-/-) mice. The expression of terminal differentiation markers and key enzymes mediating epidermal sphingolipid transport and processing in the (Epid)CaR(-/-) epidermis was significantly reduced. The (Epid)CaR(-/-) epidermis displayed a marked decrease in the number of lamellar bodies (LBs) and LB secretion, thinner lipid-bound cornified envelopes, and a defective permeability barrier. Consistent with in vivo results, epidermal keratinocytes cultured from (Epid)CaR(-/-) mice demonstrated abnormal Ca(2+)(i) handling and diminished differentiation. The impairment in epidermal differentiation and permeability barrier in (Epid)CaR(-/-) mice maintained on a low calcium (0.02%) diet is more profound and persistent with age than in (Epid)CaR(-/-) mice maintained on a normal calcium (1.3%) diet. Deleting CaR perturbs the epidermal Ca(2+) gradient and impairs keratinocyte differentiation and permeability barrier homeostasis, indicating a key role for the CaR in normal epidermal development. |
