Loss of calcineurin Aα alters keratinocyte survival and differentiation

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Calcineurin is a serine/threonine phosphatase that is inhibited by the immunosuppressive drugs cyclosporine and FK506. Although calcineurin has been extensively studied in immune cells, less is known about calcineurin in other systems. There are two primary isoforms of the catalytic subunit of calcineurin, and mice have been created that lack either the α isoform (calcineurin A (CnA)α-/-) or the ß isoform (CnAß-/-). In this study, we examined the epidermis of CnAα / mice at birth and 4 weeks of age. Histological analyses revealed an attenuation of cells in the stratum spinosum of CnAα / mice. There was no significant difference in proliferation in the epidermis of CnAα-/-sections, but TUNEL assay revealed increased cell death in the supra-basal layers. Interestingly, the calcineurin substrate nuclear factor of activated T cells (NFATc) was highly expressed in the nucleus of basal epidermal cells in wild-type (WT) mice but was cytoplasmic in CnAα-/-mice, consistent with a loss of calcineurin activity. Moreover, NFATc activity was decreased in the epidermis of null mice compared with that in WT littermates. Finally, immunohistochemical staining revealed supra-basal expression of keratin 14 and decreased expression of differentiation-associated keratin 10 and involucrin. These findings suggest that calcineurin Aα activity is required for the normal differentiation and survival of epidermal cells.

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Journal of Investigative Dermatology





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This article was published in Journal of Investigative Dermatology, Volume 130, Issue 1, Pages 135-140.

The published version is available at http://dx.doi.org/10.1038/jid.2009.222.

Copyright © 2010 Nature Publishing Group.

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